Weight loss abstract
A dietary composition is provided for promoting healthy weight
loss in cats which contains, on a dry matter basis, from about 0.2
to 1.5% by weight fatty acids selected from the group consisting
of C18:3n3, C20:4n6, C20:5n3, C22:6n3, and mixtures thereof, and
from about 28 to 50% by weight protein. The composition may be administered
to obese cats to provide optimum weight loss while preventing hepatic
lipidosis and other associated diseases.
Weight loss claims
What is claimed is:
1. A dietary composition for promoting healthy weight loss in cats
comprising, on a dry matter basis, fatty acids comprising at least
1 to 15% by weight C18, at least 0.09 to 0.5% by weight C20 and
at least 0.075 to 0.2% C22, and from about 28 to 50% by weight protein.
2. A dietary composition for promoting healthy weight loss in cats
comprising, on a dry matter basis, from about 0.2 to 1.5% by weight
fatty acids selected from the group consisting of C18:3n3, C20:4n6,
C20:5n3, C22:6n3, and mixtures thereof, and from about 28 to 50%
by weight protein, wherein the ratio of total n6 to n3 fatty acids
is from about 2:1 to 15:1.
3. The composition of claim 2 containing at least 0.04% by weight
C18:3n3.
4. The composition of claim 2 containing at least 0.045% C20:4n6.
5. The composition of claim 2 containing at least 0.04% C20:5n3.
6. The composition of claim 2 containing at least 0.075% C22:6n3.
7. The composition of claim 1 comprising from about 0.04 to 0.6%
C18:3n3, from about 0.045 to 0.3% C20:4n6, from about 0.04 to 0.2%
C20:5n3, and from about 0.075 to 0.2% C22:6n3.
8. The composition of claim 1 in which the source of said fatty
acids are selected from the group consisting of poultry fat, fish
oil, fish meal, borage oil, ground flax, and blends thereof.
9. The composition of claim 1 in which the source of protein is
selected from the group consisting of casein, chicken, turkey, beef,
lamb, and blends thereof.
10. The composition of claim 1 in which said protein has a protein
efficiency ratio of at least 2.0.
11. The composition of claim 1 comprising from about 7 to 27% by
weight total fat.
12. The composition of claim 1 comprising from about 7 to 14% by
weight total fat.
13. A dietary composition for promoting healthy weight loss in
cats comprising, on a dry matter basis, from about 28 to 50% by
weight protein, said composition containing sufficient long chain
essential fatty acids which, in combination with said protein, promotes
said healthy weight loss.
14. A dietary composition as claimed in claim 13 comprising from
about 0.045 to 0.30% by weight C20:4n6 and from about 0.075 to 0.2%
by weight C22:6n3.
15. A method of promoting weight loss in cats while preventing
hepatic lipidosis comprising the steps of:
administering an amount of a composition comprising, on a dry matter
basis, from about 0.2 to 1.5% by weight fatty acids selected from
the group consisting of C18:3n3, C20:4n6, C20:5n3, C22:6n3, and
mixtures thereof, and from about 28 to 50% by weight protein.
16. The method of claim 15 in which said composition comprises
from about 0.04 to 0.6% by weight C18:3n3, from about 0.045 to 0.3%
by weight C20:4n6, from about 0.04 to 0.2% by weight C20:5n3, and
from about 0.075 to 0.2% by weight C22:6n3.
17. A method of increasing blood plasma high density lipoprotein-cholesterol
(HDL) levels in cats comprising the step of:
administering an amount of a composition comprising, on a dry matter
basis, from about 0.2 to 1.5% by weight fatty acids selected from
the group consisting of C18:3n3, C20:4n6, C20:5n3, C22:6n3, and
mixtures thereof, and from about 28 to 50% by weight protein.
18. The method of claim 17 in which said composition comprises
from about 0.04 to 0.6% by weight C18:3n3, from about 0.045 to 0.3%
by weight C20:4n6, from about 0.04 to 0.2% by weight C20:5n3, and
from about 0.075 to 0.2% by weight C22:6n3.
19. A method of decreasing blood plasma free fatty acids levels
in cats comprising the step of:
administering an amount of a composition comprising, on a dry matter
basis, from about 0.2 to 1.5% by weight fatty acids selected from
the group consisting of C18:3n3, C20:4n6, C20:5n3, C22:6n3, and
mixtures thereof, and from about 28 to 50% by weight protein.
20. The method of claim 19 in which said composition comprises
from about 0.04 to 0.6% by weight C18:3n3, from about 0.045 to 0.3%
by weight C20:4n6, from about 0.04 to 0.2% by weight C20:5n3, and
from about 0.075 to 0.2% by weight C22:6n3.
21. A dietary composition for promoting healthy weight loss in
cats comprising, on a dry matter basis, from about 28 to 50% by
weight protein, from about 7 to 27% by weight total fat, and from
about 0.2 to 1.5% by weight fatty acids selected from the group
consisting of C18:3n3, C20:4n6, C20:5n3, C22:6n3, and mixtures thereof.
Weight loss description
BACKGROUND OF THE INVENTION
This invention relates to a dietary composition and method for
promoting healthy weight loss in cats, and more particularly, to
a dietary composition which includes a combination of fatty acids
and protein and which, when fed to cats, promotes effective weight
loss while preventing the development of diseases such as hepatic
lipidosis.
Approximately 10 to 40% of cats receiving veterinary care have
been reported to be overweight. Factors contributing to feline obesity
include a sedentary lifestyle, confinement to indoors, and neutering.
Neutered cats have a greater tendency toward weight gain, which
may be due to decreased activity and altered metabolic rates. Obese
cats have a greater risk for certain diseases including osteoarthritis,
ligament injuries, perineal dermatitis, diabetes mellitus, cardiomyopathy,
and urologic syndrome. Obese cats also appear to be particularly
susceptible to feline hepatic lipidosis, a disease characterized
by extensive lipid accumulation in liver parenchymal cells. Therefore,
it is critical to maintain a healthy weight in order to minimize
disease risk.
Safe weight loss plans must consider both the diet composition
and the rate of weight loss to minimize the risk of developing diseases
such as hepatic lipidosis. However, safe rapid weight loss in the
feline has been made difficult because of the special dietary requirements
of the cat which appear to make it more susceptible to hepatic lipidosis
than other species. For example, cats appear to require 20 carbon
long chain essential fatty acids such as 20:4n6 and 22:6n3 as they
cannot convert dietary C18 essential fatty acids into long chain
fatty acids due to a lack of .DELTA.6 desaturase. However, the dietary
levels of long chain essential fatty acids which may be needed has
not been determined.
A lack of proper essential fatty acids in the diet, or essential
fatty acid deficiency, is known to induce fatty livers in cats,
which is believed to contribute to the development of hepatic lipidosis.
Essential fatty acid deficiency is also known to affect transport
of lipoproteins (very low density lipoprotein (VLDL), intermediate
density lipoprotein (IDL), low density lipoprotein (LDL) and high-density
lipoprotein (HDL)) from the liver and lipoprotein lipase, as well
as affecting lecithin cholesterol acyltransferase and fatty acid
synthetase activities. Alterations of any of these parameters may
contribute to the development of hepatic lipidosis.
While studies have been conducted to evaluate the effect of protein
on diets designed to prevent the development of feline hepatic lipidosis,
there has been little study which addresses protein-lipid interactions
on weight loss and the development of feline hepatic lipidosis.
Further, previous studies have used primarily diets having only
single nutrients (protein, carbohydrates, fat), and have not accounted
for other nutrient deficiencies (vitamin/mineral).
Accordingly, there is still a need in the art for a dietary composition
for felines which provides safe, effective weight loss while preventing
the development of feline hepatic lipidosis (FHL) and associated
diseases.
SUMMARY OF THE INVENTION
The present invention meets that need by providing a dietary composition
for cats which includes long chain essential fatty acids and protein
in amounts which have been found to promote healthy weight loss
while preventing the development of hepatic lipidosis.
In accordance with one aspect of the present invention, a dietary
composition for promoting healthy weight loss in cats is provided
which comprises, on a dry matter basis, fatty acids comprising at
least 1 to 15% by weight C18, at least 0.09 to 0.5% by weight C20
and at least 0.075 to 0.2% by weight C22, and from about 28 to 50%
by weight protein. The designations C18, C20 and C22 are short hand
references to 18, 20 and 22 carbon long chain fatty acids. By C18
fatty acids, it is meant fatty acids including C18:2n6, C18:1, C18:3n3,
and C18:0. By C20 fatty acids, it is meant fatty acids including
C20:4n6, C20:5n3, and C20:0. By C22 fatty acids, it is meant fatty
acids including C22:6n3 and C22:1.
In a preferred embodiment of the invention, the dietary composition
comprises from about 0.2 to 1.5% by weight fatty acids selected
from the group consisting of C18:3n3 (.alpha.-linolenic acid), C20:4n6
(arachidonic acid), C20:5n3 (eicosapentanenoic acid), C22:6n3 (docosahexaneoic
acid), and mixtures thereof, and from about 28 to 50% by weight
protein. The composition preferably contains at least 0.04% by weight
C18:3n3, at least 0.045% C20:4n6, at least 0.04% C20:5n3, and at
least 0.075% C22:6n3. More preferably, the composition contains
from about 0.04 to 0.6% by weight C18:3n3, from about 0.045 to 0.3%
by weight C20:4n6, from about 0.04 to 0.2% by weight C20:5n3, and
from about 0.075 to 0.2% by weight C22:6n3. The ratio of total n6:n3
fatty acids in the composition is preferably from about 2:1 to 15:1.
The source of fatty acids is preferably selected from the group
consisting of poultry fat, fish oil, fish meal, borage oil, ground
flax, and blends thereof. The composition preferably comprises from
about 7 to 27% by weight total fat, and more preferably, about 7
to 14% by weight total fat.
Preferably, the source of protein is a high quality protein i.e.,
a protein which provides a protein efficiency rate (grams weight
gain/grams protein intake) of at least 2.0. The preferred source
of protein is preferably selected from the group consisting of casein,
chicken, turkey, beef, lamb, and blends thereof.
When the composition of the present invention is administered to
cats in a quantity and frequency appropriate for their nutritional
needs, it has been found that the cats exhibit effective weight
loss and do not develop hepatic lipidosis. We have also found that
the cats exhibit decreased free fatty acid levels and increased
high density lipoprotein-cholesterol (HDL) levels in their blood,
which levels are believed to be beneficial in preventing other diseases
associated with obesity such as heart disease.
Accordingly, it is a feature of the present invention to provide
a dietary composition and method of use for cats which promotes
healthy weight loss while preventing the development of hepatic
lipidosis. Other features and advantages of the invention will be
apparent from the following description, the accompanying drawings,
and the appended claims.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a series of bar graphs showing the effects of obesity,
weight loss and different diets on lipoprotein cholesterol concentrations;
and
FIG. 2 is a bar graph showing the effect of different diets on
liver lipid content following weight loss.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
The dietary composition of the present invention provides an improvement
over currently available dietary compositions in that the composition
uses a specific combination of fatty acids in combination with a
high quality protein to promote safe, effective weight loss in the
cat without contributing to the risk of the animal developing hepatic
lipidosis.
A study was undertaken to determine the effects of diets containing
a low (protein efficiency rate of<2.0) or high (protein efficiency
rate of>2.0) quality protein source (corn gluten meal and casein,
respectively) and their interaction with C20:4n6 and C22:6n3 deficient
(long chain essential fatty acid deficient (LCEFAD)) and C20:4n6
and C22:6n3 sufficient (long chain essential fatty acid (LCEFA))
diets fed at 25% of calculated ideal body weight maintenance energy
requirement (MaE). By "sufficient", it is
meant that the diets contained at least 0.045% by weight (on a
dry matter basis) C20:4n6 and at least 0.075% by weight C22:6n3.
By "deficient", it is meant that the diets contained less
than 0.045% by weight C20:4n6 and less than 0.075% by weight C22:6n3.
The testing procedures and results are described below. The diets
were formulated using a 2X2 factorial design as shown below in Table
1.
TABLE 1 ______________________________________ CAOB = Casein plus
blend of CGOB = Corn gluten meal plus blend poultry fat, borage
and fish oil of poultry fat, borage and fish oil (high quality protein
+ 20C (low quality protein + 20C essential fatty acid sufficient)
essential fatty acid sufficient) n = 5 n = 6 CACO = Casein plus
corn oil CGCO = Corn gluten meal plus corn oil (high quality protein
+ 20C (low quality protein + 20C essential fatty acid deficient)
essential fatty acid deficient) n = 5 n = 6 ______________________________________
Twenty-four female cats, culled breeders (Hsd Cpb:CaDs) (Harlan
Sprague Dawley, Indianapolis, Ind.), were procured. Cats were individually
housed in an AAALAC-accredited facility, and maintained on a 12--12
light dark cycle at an average room temperature of 70.degree. C.
After a one week acclimatization, they were anesthetized (ketamine,
acepromazine and isoflurane) and ovariohysterectomized. Blood samples
(10 ml) were taken two days prior to surgery and a wedge liver biopsy
was taken during surgery (all surgical procedures and animal protocol
were carried out according the "Guide for the care and use
of laboratory animals" and Institutional Animal Care and Use
Committee approved). Prior to surgery cats were fed a commercial
laboratory cat diet and water ad libitum. Following surgery, cats
were fed a high quality energy dense diet (Eukanuba Veterinary Diets.RTM.,
Nutritional Recovery Formula and Ocean Fish Formula Cat Food, The
lams Company, Dayton, Ohio) ad libitum until they gained a minimum
of 30% over their ideal weight. Once the animals attained at least
30 percent body weight gain, they were assigned randomly to one
of four treatment groups (6 animals/treatment) in staggered intervals
(4 animals/week; 1/each treatment/week)(See Table 1). Blood samples
(10 ml) were taken again two days prior to obtaining a wedge liver
biopsy. The cats were maintained on the various weight reduction
diets for 7-8 weeks, or until they reached body weights similar
to but not less than -10% of the ideal body weight established for
healthy cats of the same body type and length. When the cats attained
the desired body weights, liver biopsies and blood samples were
obtained (blood samples were also taken after 21 days on the various
weight reduction diets). If any of the cats had a bilirubin level>0.4
mg/dl during the weight loss period, they were to be discontinued
from the study.
When placed on the weight reduction diet, one cat refused to eat
due to a broken tooth and gum inflammation; this cat voluntarily
remained in a fasted condition even after the tooth problem was
corrected and ultimately developed feline hepatic lipidosis. Data
are provided for this cat to contrast with the other weight loss
groups.
All of the experimental diets were formulated and provided by The
lams Company, Dayton, Ohio. The composition of the diets fed during
the weight reduction is shown in Tables 2 and 3 below.
TABLE 2 ______________________________________ Composition of Diets
Fed to Obese Cats at 25% of Maintenance Energy for Weight Reduction
CGCO CGOB CACO CAOB Corn gluten Corn gluten Casein/ Casein/ meal/corn
oil meal/oil blend corn oil oil blend ______________________________________
Ingredients (%) Corn gluten meal 68.30 68.30 Casein 52.00 52.00
Corn oil 13.00 18.70 3.90 Poultry fat 11.70 13.50 Corn starch 5.00
5.00 19.60 19.60 Calcium carbonate 3.70 3.70 0.02 Dried beet pulp
3.00 3.00 3.00 3.00 Monosodium 2.40 2.40 0.49 0.49 phosphate Choline
chloride 1.50 1.50 1.80 1.80 Minerals 1.20 1.20 1.20 1.20 Vitamins
1.20 1.20 1.20 1.20 Sodium chloride 1.00 1.00 DL-methionine 0.32
0.32 Fish oil 0.90 0.90 Borage oil 0.15 0.15 Ground flax 0.15 0.15
Taurine 0.15 0.15 0.15 0.15 Potassium chloride 0.49 0.49 0.54 0.61
Nutrients Protein % (4 kcal/g) 45.09 44.37 42.97 41.94 Moisture
% 5.81 7.62 10.28 10.85 Ash % 7.87 7.98 7.36 7.06 Fat % (9 kcal/g)
17.18 17.29 17.1 18.51 Crude fiber % 2.22 2.34 2.28 1.59 N-free
extracts (%) 21.84 20.4 19.79 19.97 (4 kcal/g) Calculated energy
4223 4146 4049 4142 (kcal/kg) ______________________________________
TABLE 3 ______________________________________ Fatty Acid Composition
of Diets (expressed as % by weight of total diet composition) CGCO
CGOB CACO CAOB Corn Gluten Corn gluten Casein/ Casein/ Fatty Acids
Meal/corn oil meal/oil blend corn oil oil blend ______________________________________
C 16:1 0.49 0.47 C 16:0 0.79 2.24 0.79 2.25 C 18:2n6 10.29 4.36
10.76 5.45 C 18:1 4.62 7.43 4.77 7.89 C 18:3n3 0.53 0.40 C 18:0
0.37 1.13 0.38 1.15 C 20:4n6 0.05 0.05 C 20:5n3 0.03 0.14 0.04 0.15
C 20:0 0.09 0.02 0.10 0.04 C 22:6n3 0.19 0.16 C 22:1 0.03 0.04 0.04
C 24:1 0.03 0.03 C 24:0 0.05 0.03 0.04 0.02 ______________________________________
Diets were fed at 25% of ideal lean bodyweight maintenance energy
requirement (MaE) according to the following formula: {[(ideal bodyweight
kg.times.30 kcal/kg)+70].times.1.4 activity factor}/4=25% MaE in
kcal. Vitamins, choline, taurine and micro-minerals were supplemented
at 4 times the NRC requirements so that animals consuming 25% MaE
would be supplied with the normally required NRC amounts.
The protein efficiency ratio (PER=grams weight gain/grams protein
intake) of the casein and corn gluten meal was determined using
a ten day chick growth assay (Research and Development, The lams
Company, Lewisburg, Ohio). Day old male Hubbard broilers were fed
an 18.5% crude protein commercial corn-soy starter diet for 7 days
prior to initiation of the study. Egg protein was included as a
standard in the assay. Birds were allotted to dietary treatment
groups so that average body weights of chicks in each group were
similar. Each treatment contained 5 replicates of 7 birds and each
replicate of 7 birds was maintained as the experimental unit. All
chicks were housed in thermostatically controlled starter batteries
with raised wire floors in an environmentally regulated room and
allowed ad libitum access to water and feed for the duration of
the study. Test ingredients were included in an amount necessary
for finished diets to contain 9% crude protein. The basal portion
of each diet included dextrose (30%), corn oil (5%), glista salts
(5.37%), choline chloride (0.20%), a commercial vitamin premix (0.20%),
and corn starch to 100%. Feed consumption and body weights were
measured during the 10 day growth period to determine PER.
Measurements and Collections
Body weights were recorded weekly and chest girth prior to and
after the weight reduction period.
Blood samples (10 ml/collection period) were taken from the jugular
vein of sedated cats (medetomidine hydrochloride, 0.3 ml and atopanezole
hydrochloride, sc) at 1) baseline, 2) following a minimum 30% weight
gain, 3) after 21 days and 4) approximately 49 to 63 days on the
weight loss diets (time varied per individual cat to attain the
calculated 30% weight loss). Samples were drawn into glass vacutainer
tubes with or without EDTA for plasma or serum. following a 16 hour
fast. Samples were centrifuged at 4.degree. C. and the serum or
plasma samples stored at -70.degree. C. prior to analysis.
Liver biopsies were performed on the anaesthetized cats as a wedge
biopsy at the beginning of the protocol (during the ovariohysterectectomy
procedure), after the cats attained a minimum of 30% weight gain,
and then following the loss of at least 30% of body weight. Liver
samples were fixed in phosphate-buffered 10% formalin for assessment
of histopathology using light microscopy or extracted into hexane-isopropanol
(3:2 vol) for lipid analysis.
To determine fatty liver content, a portion of the liver samples
were weighed, extracted with hexane isopropanol (3:2 volume), dried
under nitrogen and the lipid content expressed on a liver dry weight
basis. Another portion of the liver was fixed with 10% buffered
formalin, paraffin embedded, sectioned and stained with H&E
and osmium tetroxide for assessing neutral lipids using normal laboratory
procedures.
Slides were digitized using a Zeiss (Germany) microscope connected
to image processing software (NIH IMAGE 1.60). Threshold optical
density values were set to blank out non-specific staining. Optical
density units thus directly correlate with the intensity of neutral
lipid staining and are expressed as % optical density/mm. Values
were also expressed on a 1 to 6 scale with 1 to 2 considered normal,
3 to 4 having mildly increased lipid staining, 5 showing definite
lipid accumulation and 6 equal to severe lipidosis; all samples
were assessed with the operator blinded to the sample origin.
Electron microscopic analysis of representative liver samples was
also conducted. Tissue samples (1 mm) were immersed in a solution
containing 4% paraformaldehyde (Sigma, St Louis, Mo. U.S.A.) and
0.5% glutaraldehyde in 0.14 mol/l phosphate buffer, at pH 7.0, for
several weeks. After thorough washing in the same buffer, the samples
were postfixed in 2% osmium tetroxide (Electron Microscopical Sciences,
Fort Washington, Pa.), dehydrated in a series of ethanol, then embedded
in Durcupan resin (Fluka, Buchs, Switzerland). Sixty run ultra-thin
sections were cut with a diamond knife on a Reichert-Jung Ultracut
E ultramicrotome (Vienna, Austria). The ultra-thin sections were
contrasted with lead citrate (Ted Pella, Inc., Redding, Calif.,
U.S.A.) and uranyl acetate (Merck, Darmstadt, Germany), then viewed,
and photographs taken using a JEOL 200CX electron microscope (Tokyo,
Japan). The sections were analyzed as follows: 10 cell profiles/section/sample
were counted and the number of lipid inclusions and peroxisomes
(small, round, about 250-500 nm in diameter, with crystalloid inclusions)
were determined/cell profile. The average for all profiles was then
calculated.
Biochemical assessment was done on plasma samples at baseline,
following maximum weight gain, 21 days after starting the weight
reduction feeding protocol and at the end of weight reduction period
(Vet panel 1--Roche Cobas Mira, Roche Diagnostics Systems, Somerville,
N.J.). Serum insulin was determined by using an insulin coated tube
radioimmunoassay according to a previously reported procedure which
has been validated for the feline 21 (IVDL, Inc., Fishers, Ind.).
Statistical Analysis Data were analyzed by two way analysis of
variance (ANOVA) followed by least square means analysis (LSM) to
measure significant differences between treatment groups. Differences
between means were considered significant at p<0.05 (SYSTAT 7.0,
SYSTAT, Inc. Evanston, Ill.).
Lipoprotein cholesterol and triglycerides were measured enzymatically
using cholesterol and triglyceride kits (Sigma Chemical Co., U.S.A.).
To prepare VLDL, 400 .mu.l of plasma was transferred to a polycarbonate
tube (11.times.34 mm) and overlayed with 600 .mu.l of d=1.006 KBr
solution, and submitted to ultracentrifiugation (2 h, 15.degree.
C., 435,680.times.g). The VLDL in the top 400 .mu.l of each tube
was harvested by aspiration. To prepare intermediate density lipoprotein-cholesterol
(IDL), the density of the lower fraction was adjusted to 1.019 g/ml
by adding 24.3 .mu.l of d=1.34 solution and the final volume brought
to 1 ml with d=1.019 solution. Centrifugation was performed as described.
The IDL in the top 400 .mu.l of each tube was harvested by aspiration.
To prepare LDL, 600 .mu.l of the lower fraction was mixed with
95.3 .mu.l of d=1.34 solution and 304.7 .mu.l of d=1.063 solution
and centrifuged for 2.5 hours (same temp and g); 400 .mu.l of each
tube was harvested by aspiration.
To prepare HDL, the density of 600 .mu.l of the lower fraction
was adjusted to 1.21 g/ml by adding 678.5 .mu.l of d=1.34 solution.
The sample was brought to a final volume of 1.3 ml with 21.5 .mu.l
of d=1.21 solution. Only 1 ml of the mixture was submitted to ultracentrifugation
(3 h, same temp and g). A correction factor of 1/3 is needed to
determine the concentration of the various analytes in the 400 .mu.l
of supernatant
containing HDL.
Results
Weight Gain and Weight Loss
As shown in Table 4 below, the cats gained approximately 4.7 grams
per day following the ovariohysterectomy until 80 days post surgery
at which time no further weight gain was noted up to 108 days. Irrespective
of the different diets fed at 25% of the MaE, all cats lost weight
at a comparable rate (4.51-5.00 g/day/kg obese bodyweight) averaged
over the entire weight loss period; the greatest rate of weight
loss occurred during the first week of the diet (See Table 5);
there were no significant differences between the treatment groups.
The cats lost about 7 to 10% of their obese bodyweight during the
first week, 3 to 5% during the second week and 2 to 4% per week
during the remainder of the weight loss period. The cat which voluntarily
fasted lost weight at a greater rate (average 7.07 g/day/kg obese
bodyweight or 5% bodyweight/week) than the cats maintained on 25%
of the MaE (average 4.26 g/day/kg obese bodyweight or 3.3% bodyweight
/week).
TABLE 4 ______________________________________ Effect of Ovariohysterectomy
on Body Weight Changes of Cats Body weight Body weight (Mean .+-.
SD) (Mean .+-. SD) Days After Surgery (kg) (n = 24) (% of ideal)
______________________________________ 0 2.91 .+-. 0.57 100 .+-.
19.58 4 2.90 .+-. 0.41 99.65 .+-. 14.08 20 3.08 .+-. 0.58 105.84
.+-. 19.93 36 3.41 .+-. 0.57 117.18 .+-. 19.58 51 3.61 .+-. 0.57
124.05 .+-. 19.58 67 3.64 .+-. 0.53 125.08 .+-. 18.21 81 4.02 .+-.
0.69 138.14 .+-. 23.71 108 3.95 .+-. 0.75 135.73 .+-. 25.77 ______________________________________
TABLE 5 __________________________________________________________________________
Body Weight Changes of Cats on Weight Reducing Diets CGCO CGOB CACO
CAOB Corn gluten Corn gluten Casein/ Casein/ Voluntarily Meal/corn
oil Meal/Oil blend Corn oil Oil Blend Days on Weight Fasting Cat
(Mean .+-. SD) (Mean .+-. SD) (Mean .+-. SD) (Mean .+-. SD) Reducing
Diets (n = 1) (n=6) (n = 6) (n = 5) (n = 5) __________________________________________________________________________
(kg) 5.05 4.00 .+-. 0.56 3.82 .+-. 0.71 3.57 .+-. 0.43 3.31 .+-.
0.70 (%) of obese 100.00 100.00 .+-. 15.24 100.00 .+-. 18.49 100.00
.+-. 12.00 100.00 .+-. 20.98 7 (kg) 4.67 3.74 .+-. 0.50 3.57 .+-.
0.69 3.26 .+-. 0.49 3.07 .+-. 0.63 (%) of obese 92.48 93.66 .+-.
13.57 93.5 .+-. 18.18 91.16 .+-. 13.70 90.80 .+-. 19.0 14 (kg) 4.42
3.60 .+-. 0.47 3.40 .+-. 0.70 3.10 .+-. 0.42 2.95 .+-. 0.61 (%)
of obese 87.52 89.95 .+-. 12.91 89.05 .+-. 18.22 86.85 .+-. 11.76
88.19 .+-. 18.50 21 (kg) 4.12 3.44 .+-. 0.47 3.27 .+-. 0.70 2.98
.+-. 0.41 2.83 .+-. 0.58 (%) of obese 81.58 85.95 .+-. 12.87 85.48
.+-. 18.42 83.49 .+-. 11.44 83.55 .+-. 17.53 28 (kg) 3.90 3.33 .+-.
0.46 3.17 .+-. 0.66 2.90 .+-. 0.40 2.73 .+-. 0.56 (%) of obese 77.23
83.32 .+-. 12.51 82.86 .+-. 17.30 81.14 .+-. 11.17 80.83 .+-. 16.96
35 (kg) 3.72 3.23 .+-. 0.45 3.08 .+-. 0.66 2.80 .+-. 0.39 2.65 .+-.
0.55 (%) of obese 73.66 80.73 .+-. 12.46 80.46 .+-. 17.14 78.29
.+-. 10.99 79.02 .+-. 16.58 42 (kg) 3.46 3.16 .+-. 0.44 2.98 .+-.
0.65 2.72 .+-. 0.39 2.57 .+-. 0.52 (%) of obese 68.51 78.98 .+-.
11.95 77.98 .+-. 17.06 76.22 .+-. 11.03 75.32 .+-. 18.80 49 (kg)
3.30 3.06 .+-. 0.42 2.89 .+-. 0.61 2.64 .+-. 0.39 2.50 .+-. 0.50
(%) of obese 65.35 76.65 .+-. 11.51 75.67 .+-. 16.07 73.92 .+-.
10.99 72.52 .+-. 15.22 56 (kg) 2.99 .+-. 0.41 2.81 .+-. 0.62 2.57
.+-. 0.40 2.43 .+-. 0.49 (%) of obese 74.90 .+-. 11.18 73.57 .+-.
16.27 71.91 .+-. 11.32 70.39 .+-. 14.77 63 (kg) 2.90 .+-. 0.40 2.89
.+-. 0.51 2.62 .+-. 0.37 2.35 .+-. 0.46 (%) of obese 72.64 .+-.
10.85 71.93 .+-. 12.61 73.13 .+-. 10.42 65.76 .+-. 13.80 (n = 5)
__________________________________________________________________________
Changes in chest girth prior to and after the weight loss period
were similar between the treatment groups. However, the obese animals
had significantly greater chest girth (32.0.+-.2.2 cm) than following
the weight loss period (27.8.+-.1.5 cm). The average body length
of the cats was 42.6.+-.1.9 cm.
Protein Efficiency Ratio
The PER (grams weight gain/grams protein intake) for the diets
fed were measured to be as follows: Casein/oil blend (CAOB)=2.3,
Casein/corn oil (CACO)=3.0, Corn gluten meal/oil blend (CGOB)=11
and Corn gluten meal/corn oil (CGCO)=1.4.
Serum Lipids and Biochemistry
There were significant changes in serum lipid levels and other
biochemical parameters due to weight gain and weight loss for all
the treatment groups, but there were no significant differences
noted between any of the dietary treatment groups. The serum biochemistry
data for the weight loss period for all the treatment groups are
combined and the data are shown in Table 6 below.
TABLE 6 __________________________________________________________________________
Biochemistry of Cats Prior to Weight Gain (Baseline), at a Minimum
of 30% Weight Gain Above Baseline (Obese), after 21 days on weight
reduction diets (21.sup.st day), and following at least 30% weight
loss (final) Baseline Obese 21.sup.st Day Final __________________________________________________________________________
Cholesterol (mg/dL) 107.52 .+-. 23.78 193.39 .+-. 45.18 117.13 .+-.
22.82 154.27 .+-. 35.74 Triglyceride (mg/dL) 48.61 .+-. 37.2 60.65
.+-. 38.2 42.52 .+-. 14.03 38.18 .+-. 19.56 Total bilirubine (mg/dL)
0.17 .+-. 0.19 0.10 .+-. 0.06 0.069 .+-. 0.05 0.062 .+-. 0.05 Glucose
(mg/dL) 139.39 .+-. 54.73 201.61 .+-. 73.46 154.7 .+-. 50.48 225.41
.+-. 75.98 Insulin (mU/L) 2.65 .+-. 2.49 2.55 .+-. 1.87 2.31 .+-.
1.85 6.53 .+-. 4.82 Uric acid (mg/dL) 0.31 .+-. 0.14 0.09 .+-. 0.06
0.09 .+-. 0.07 0.44 .+-. 0.24 ALT (IU/L) 78.61 .+-. 40.61 73.13
.+-. 33.59 62.82 .+-. 31.94 48.77 .+-. 25.86 AST (IU) 32.82 .+-.
9.94 30.32 .+-. 14.45 23.72 .+-. 8.02 22.76 .+-. 11.04 LDH (IU)
131.41 .+-. 52.29 115.55 .+-. 49.69 94.77 .+-. 44.35 129.82 .+-.
72.29 Alkaline Phosphatase (IU) 22.21 .+-. 9.90 32.47 .+-. 11.01
28.69 .+-. 9.26 14.09 .+-. 9.04 Creatin Kinase (IU) 437.61 .+-.
281.60 145.17 .+-. 131.02 80.65 .+-. 30.50 188.18 .+-. 141.05 Creatinine
(mg/dL) 1.47 .+-. 0.20 2.00 .+-. 0.22
1.96 .+-. 0.20 1.62 .+-. 0.31 Blood Urea Nitrogen 20.48 .+-. 3.64
26.17 .+-. 4.00 20.61 .+-. 2.66 25.00 .+-. 4.35 (mg/dL) Total Protein
(g/L) 6.27 .+-. 0.49 6.55 .+-. 0.48 6.09 .+-. 0.44 5.87 .+-. 0.73
Albumin (g/L) 3.15 .+-. 0.40 3.46 .+-. 0.32 3.42 .+-. 0.22 3.00
.+-. 0.24 Globulin (g/L) 3.12 .+-. 0.37 3.09 .+-. 0.53 2.67 .+-.
0.40 2.86 .+-. 0.68 Ca (mg/dL) 9.53 .+-. 0.89 9.81 .+-. 0.57 9.86
.+-. 0.35 9.12 .+-. 0.39 P (mg/dL) 4.55 .+-. 0.99 5.24 .+-. 0.67
4.93 .+-. 0.51 4.61 .+-. 0.53 Mg (mg/dL 2.13 .+-. 0.16 2.17 .+-.
0.25 2.11 .+-. 0.25 1.96 .+-. 0.26 Na (mEqu/L) 154.48 .+-. 2.64
155.48 .+-. 5.74 156.22 .+-. 5.37 153.32 .+-. 8.42 K (mEqu/L) 3.94
.+-. 0.36 4.26 .+-. 0.46 3.72 .+-. 0.62 4.70 .+-. 0.59 Cl (mEqu/L)
121.26 .+-. 2.47 121.22 .+-. 6.25 122.61 .+-. 6.33 124.27 .+-. 8.99
__________________________________________________________________________
Serum cholesterol concentration was significantly elevated in the
obese group compared to baseline, 21 day and the final weight loss
period. There was no significant difference between baseline and
the 21 day weight loss group whereas the final weight loss period
differed significantly from both groups. Triglyceride values were
also significantly elevated in the obese group compared to the 21
day and final weight loss groups. However, unlike cholesterol values,
the triglyceride concentration was not significantly elevated at
the end of the weight loss period and was not significantly different
from the baseline value.
VLDL-Cholesterol
As shown in FIG. 1, there was a significant increase in plasma
VLDL-cholesterol in the obese versus baseline and all weight loss
dietary treatment groups. Comparing the dietary treatment groups,
at the end of the weight loss period, the VLDL concentration in
the CAOB group was significantly less then the CACO group. VLDL-triglyceride
was also measured at baseline, following weight gain and after the
weight loss on the various dietary treatments and the changes noted
were similar to VLDL-cholesterol except that a significant difference
was noted between the CAOB and the CGCO group (VLDL-triglyceride
in mg/dl: BL=6.98.+-.2.02; OB=7.64.+-.1.92; CAOB=5.59.+-.1.195;
CACO=4.91.+-.0.946; CGOB=5.05.+-.0.86;
CGCO=4.25.+-.1.24). There were no significant oil or protein effects
or oil-protein interactions regarding VLDL-cholesterol or triglyceride
noted.
IDL-Cholesterol
Significant oil effects were noted for IDL. As depicted in FIG.
1 there was a significant, almost 4 fold, increase in IDL for the
obese versus baseline and final weight loss dietary treatment groups.
Furthermore, there were significant differences noted between the
dietary treatments. The IDL concentration for the CAOB group was
significantly different from the CACO and CGCO groups.
LDL-Cholesterol
There were no significant oil or protein effects or oil-protein
interactions regarding LDL-cholesterol. Again, the obese group had
significantly higher plasma LDL cholesterol concentrations versus
baseline or dietary treatment groups (FIG. 1). CGOB was found to
be significantly different from CACO.
HDL-Cholesterol
A main effect due to oil was found to be highly significant with
a protein effect approaching significance (p=.0502); there was no
significant interaction between oil and protein. The obese group
showed significantly elevated HDL-cholesterol concentrations versus
baseline. CGOB HDL-cholesterol concentrations were significantly
greater than CACO and CGCO.
Plasma Free Fatty Acid (FFA)
No significant oil or protein effects were noted, however there
was a significant protein and oil interaction. FFA in the CGCO group
was significantly higher than the CAOB group. The cats which developed
lipidosis (LIP) were shown to have significantly elevated FFA over
all other dietary treatment groups prior to and following rapid
weight loss.
Hepatic Lipidosis
Three cats developed hepatic lipidosis during the weight loss period
as determined by liver lipid content (data not shown); one animal
in the CAOB group consumed only 12% of maintenance energy requirement,
one animal in the CACO refused to eat and one animal in the CGCO
group developed hepatic lipidosis when consuming 25% of maintenance
energy requirement.
Liver Lipids
As shown in FIG. 2, the liver lipid content, as % of dry matter,
was significantly altered by the dietary treatments during the weight
loss period. There was also a significant protein effect. The liver
lipid content was significantly higher in the corn gluten meal/corn
oil group than in the casein/oil blend and the casein/corn oil supplemented
animals; however, the corn gluten/corn oil group was not significantly
different from the corn gluten meal/oil blend treatment.
Histology
The changes in liver triglycerides (expressed as % change from
baseline values and final values minus obese values based on osmium
tetroxide lipid staining particles) are shown in Table 7 below.
TABLE 7 ______________________________________ Percent Change of
Lipid Particles from Baseline in Cat Liver Sections Stained with
Osmium Tetroxide Baseline 100 100 100 100 ______________________________________
Obese (Mean .+-. SD) 181 .+-. 107 120 .+-. 27 163 .+-. 123 256 .+-.
101 Diet Treatments Casein/ Casein/ Corn Gluten/ Corn Gluten/ Oil
Blend Corn Oil Oil Blend Corn oil Final (Mean .+-. SD) 170 .+-.
24 185 .+-. 42 190 .+-. 58 350 .+-. 141 Final - Obese -11 65 27
94 ______________________________________
There were no significant differences noted between dietary groups.
In comparing the combined obese versus baseline values there was
significantly more liver lipid accumulation in the obese group (data
not shown). During the fasting period the liver triglycerides were
increased more in the corn oil supplemented groups versus the oil
blend groups. The group having the most liver triglycerides (obese
and final values) was the corn gluten meal/corn oil group. Only
in the corn gluten meal/corn oil group did any of the animals show
histopathologic changes and other symptoms associated with feline
hepatic lipidosis (FHL).
It was noted that the animal showing symptoms of FHL and lipid
accumulation in the liver, from the corn gluten meal/corn oil group,
also exhibited a marked reduction, or a complete absence, of peroxisomes
compared to a cat from the casein/corn oil group. Furthermore, many
of the lipid droplets in the FHL cat livers were heterogeneous in
size and electron density, inclusion bodies were present, and the
fine structural changes suggested an alteration in lipid and protein
metabolism.
Discussion
The body weight gains of the cats increased consistently following
ovariohysterectomy until 80 days post surgery after which the weights
reached a new plateau (set point) and no further weight gain was
observed up to 108 days in most animals; it is well documented that
neutering an animal contributes to weight gain. Total weight loss
and the rate of weight loss on the 25% MaE diets showed no significant
differences between the dietary groups during the weight loss period,
suggesting that neither low or high quality protein and/or dietary
LCEFA status markedly alter weight loss patterns during this period.
The cats lost about 7 to 10% of their obese body weight during the
first week to 5% during the second week and 2 to 4% per week during
the remainder of the weight loss period. The current diets, which
varied in protein quality, provided approximately one half the amount
(2 grams protein/kg bodyweight/day) reported to maintain greater
than 80% of lean body mass. Although we did not directly measure
lean body mass, the animals in the casein/oil blend, casein/corn
oil, and corn gluten meal/oil blend groups all appeared healthy
from both a visual and biochemical assessment throughout most of
the weight loss period (insulin and glucose were elevated at the
end of the weight loss period).
It is apparent from the data that obese cats had significantly
higher serum cholesterol concentrations compared to baseline values.
Following 21 days of weight loss, the cholesterol values decreased
in all dietary groups and then increased with the continued weight
loss. Triglyceride (TG) concentrations were also significantly different
comparing the obese to the final weight loss group.
The changes in triglyceride and cholesterol concentrations in the
study, while showing significant changes with duration of the weight
loss period, were within normal ranges reported for the feline.
These changes in total cholesterol concentration might be related
to 1) increased cholesterol synthesis rates to provide for greater
steroid hormone production during the continued catabolic state,
2) decreased clearance of LDL from circulation due to LDL receptor
down regulation, 3) decreased HDL clearance or increased HDL production
which may be associated with greater cellular breakdown and increased
reverse cholesterol transport, and/or 4) diminished protein stores
resulting in altered apoprotein synthesis. The data in Table 6 indicate
that serum protein concentration is significantly reduced during
the weight reduction period.
With the exception of the voluntarily fasting cat and a cat from
the corn gluten meal/corn oil group, none of the animals developed
overt symptoms or biochemical or histologic changes characteristic
of FHL. However, as shown in FIG. 2 and Table 7, alterations in
liver lipid content did occur with respect to the diets fed. The
most lipid accumulation, assessed histologically and gravimetrically,
occurred in the corn gluten meal/corn oil group, suggesting that
poor protein quality and the absence of LCEFAs are involved in development
of FHL.
The data suggest that greater accumulation of liver lipids during
the weight gain period may be associated with, or contribute to,
the development of FHL during a rapid weight loss period since the
obese animals randomly assigned to the corn gluten meal/corn oil
diet showed the highest liver lipid levels (Table 7). The mechanism(s)
are not clear but may be associated with the changes in peroxisome
numbers and the ability of the animal to oxidize longer chain fatty
acids. Liver peroxisomes were absent in the cat that developed FHL
in the corn gluten meal/corn oil versus a normal cat liver from
the casein/corn oil fed group. The decline in peroxisome numbers
appears to be related to the duration of the fast.
The increased liver lipids in FHL may be due to decreased transport
from the liver in the form of VLDL. However, as shown in FIG. 1,
it is evident that there is a significant decrease in VLDL-cholesterol
in the weight loss groups compared to obese; the only significant
difference between groups was the CACO vs CAOB groups. The animals
which developed lipidosis also exhibited similar VLDL-cholesterol
levels, suggesting that plasma VLDL concentrations are not altered
in FHL.
It was noted that there was a significant oil effect regarding
HDL. The oil blend groups had higher HDL plasma concentrations than
the corn oil groups with the CGOB group being significantly higher
than the CGCO group. The significant changes in total plasma cholesterol
concentrations noted for the baseline versus obese and the obese
versus weight loss groups is due primarily to changes in HDL. VLDL,
IDL and LDL lipoprotein fractions returned to baseline values following
rapid weight loss but the HDL concentration was further increased
at this time period. Cholesterol concentration also increased during
the shorter weight loss period both in lean as well as obese animals.
It appears that an oil blend diet may be more beneficial than the
corn oil diet since the HDL in the oil blend groups was significantly
higher than in the corn oil groups.
The data suggest that neither increased triglyceride synthesis
nor decreased VLDL transport from the liver is the primary mechanism
involved in the development FHL during a rapid weight loss period.
Therefore the mechanism(s) involved in the development of FHL are
not clear but may be associated with increased mobilization of lipid
stores. This is supported by the significantly higher FFA found
in the cats which developed lipidosis and the somewhat higher FFA
in the CGCO group.
The data further indicates that the interaction of dietary protein
and lipid content has a greater effect on the cholesterol profile
(see FIG. 1) than dietary protein or lipids alone.
Based on this data, the dietary composition of the present invention
was formulated and preferably contains from about 0.2 to 1.5% by
weight fatty acids selected from the group consisting of C18:3n3,
C20:4n6, C20:5n3, and C22:6n3, and mixtures thereof, and from about
28 to 50% by weight high quality protein.
We have found that a 25 to 30% weight loss can be accomplished
without any overt signs of developing feline hepatic lipidosis as
long as the composition contains a high quality protein, includes
the preferred amounts of long chain fatty acids, and is fortified
with vitamins and micro-minerals so that the amount of diet consumed
meets the vitamin and
micro-mineral requirements of the cat. In addition to the preferred
concentration of fatty acids, it should be understood that the composition
may contain additional long chain fatty acids such as those listed
in Table 3. For example, the composition preferably contains from
about 4 to 7% by weight C18:2n6, from about 6 to 9% C18:1, and from
about 0.5 to 2% by weight C18:0.
The dietary composition may be provided in any suitable form as
long as it contains the preferred concentrations of fatty acids
and protein on a dry matter basis. For example, the composition
may be extruded and canned or provided in biscuit form.
The source of fatty acids in the composition preferably comprises
a blend of poultry fat and one or more of fish oil, fish meal, borage
oil, and ground flax. This blend of fats is believed to provide
a fatty acid profile which provides safe weight loss. Preferably,
the fatty acid blend comprises from about 0.04 to 0.6% C18:3n3 (.alpha.-linolenic
acid), from about 0.045 to 0.3% C20:4n6 (arachidonic acid), from
about 0.04 to 0.2% C20:5n3 (eicosapentaenoic acid), and from about
0.075 to 0.2% C22:6n3 (docosahexaenoic acid). These fatty acids
preferably comprise from about 0.2 to 1.5% of the total composition
on a dry matter basis.
The source of protein preferably comprises casein, but may comprise
other sources of protein such as chicken, turkey, egg, beef, lamb,
etc. as long as they provide a protein efficiency ratio of at least
2.0.
While certain representative embodiments and details have been
shown for purposes of illustrating the invention, it will be apparent
to those skilled in the art that various changes in the methods
and apparatus disclosed herein may be made without departing from
the scope of the invention, which is defined in the appended claims.
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