Increased Adipose Tissue Mass Research Articles

Body composition of lambs receiving 30 or 60 days of exercise training and (or) fenoterol treatment

The interaction between exercise and the β-adrenergic agonist, fenoterol, on body composition and muscle protein turnover was studied in this investigation. Forty young Hampshire × Rambouillet lambs were assigned to control (CON), exercised (EX), fenoterol-treated (5 ppm) (FEN), or fenoterol-treated and exercised (FENEX) groups. Lambs assigned to the exercise treatments were trained to run on a 10° inclined treadmill. The lambs were slaughtered after 30 or 60 days of treatment. Average daily gain tended ( p=0.09) to be greater, and feed:gain was significantly lower ( p=0.03) in the EX group than in the FENEX group by 30 days of treatment. By 60 days of treatment, kidney and pelvic fat and bodywall thickness were least in the EX group. Leg weights increased significantly with time only in the FEN and FENEX groups, whereas shoulder weights increased with time in all but the EX group. The latter effect was due to a cessation of adipose tissue growth in the EX lambs. There were significant time × treatment effects for the M. biceps femoris, M. gluteus medius, M. quadriceps femoris, M. semimembranosus, M. semitendinosus, M. infraspinatus, and M. pectoralis profundus. In every case, the time × treatment interaction was caused by nonsignificant growth of muscles in the CON group between 30 and 60 days. For the M. biceps femoris, M. quadriceps femoris, and M. gluteus medius, muscle mass increased with time only in the FENEX lambs. There was no increase in leg subcutaneous or intermuscular adipose tissue mass between 30 and 60 days in the EX lambs, although 50–70% increases in adipose tissue mass were observed over time in the other groups. Calpain and calpastatin activities in M. biceps femoris were not affected by treadmill exercise, fenoterol administration, or time × treatment ( p > 0.72 for all effects). Myosin light chain-1 gene expression in the FENEX lambs was depressed by 60 d, suggesting that the rate of M. biceps femoris growth in this treatment group was slowing by this time.

Pharmacological treatment of obesity: therapeutic strategies.

Obesity is now a common disorder in the industrialized world.1 Much has been reported during the past several years in the popular press about the increasing incidence of obesity and the comorbidity of associated conditions. In addition, there have recently been fundamental advances in our understanding of factors which mediate hunger and satiety and those involved with energy utilization and storage. In this Perspective, we summarize the present state of research in the field of therapeutics targeted for obesity, including promising new approaches for the future. Obesity is a chronic condition characterized by an overabundance of adipose tissue and can be measured in a variety of different ways.2 Excess energy is stored in the form of triglycerides in adipose tissue, and increased adipose tissue mass can occur through increases in cell size, cell number, or both. Increased adipose cell size alone results in hypertrophic obesity which is relatively mild. Increased fat cell number, however, causes hyperplastic obesity characteristic of a more severe condition. While the volume of lipid an individual adipocyte can accumulate is finite, the capacity of adipose tissue to expand is virtually limitless. The most common obesity measure is the body mass index or BMI, defined as weight in kilograms divided by (height in meters)2. BMI values are easy to calculate and correlate well with rankings obtained from more sophisticated techniques and the cormorbidities associated with obesity. It is difficult to set a definitive BMI level threshold to define obesity, particularly for women in which excess weight is often found in the pelvis and not in the abdomen. For example, the BMI scale does not take the distribution of body fat or lean muscle mass into account. Nevertheless, obesity is defined by the World Health Organization as a BMI of 30.0 kg/m2 and above, with a BMI of 25.0-29.9 kg/m2 classified as overweight or preobese.3 A large body of epidemiological data correlates increased body weight with risks such as high blood pressure, coronary heart disease, diabetes, altered steroid metabolism, gallstones, and certain forms of cancer.4 In one study, involving a cohort of >115 000 female nurses over a period of 14-16 years, increased risks of cardiovascular disease and cancer were observed with increasing BMI. Excluding smokers from all groups, there was a 100% greater risk of death from all causes for a BMI of >29.0 kg/m2 relative to the risk of death for slender women (BMI of <19.0 kg/m2) during the course of the study.5 On the basis of an increasing awareness of the public health risks associated with excess weight, the American Heart Association has recently reclassified obesity as a “major, modifiable risk factor for coronary heart disease”.6 Second only to smoking, obesity is a major threat to the public health with ca. 300 000 deaths attributed annually in the United States.1,7 Our understanding of the prevalence of obesity in the U.S. population has come largely from the four cycles of the National Health and Nutrition Examination Surveys, conducted by the National Center for Health Statistics.8 In 1994, 55% of the population was considered overweight and 22.5% were obese. These alarmingly high levels represent a marked increase from previous years and are accompanied by a worldwide * Address correspondence to either author. A. B. Reitz: tel, 215628-5615; fax, 215-628-4985; e-mail, areitz@prius.jnj.com. C. P. Kordik: tel, 215-628-7986; fax, 215-628-4985; e-mail, ckordik@prius.jnj.com. © Copyright 1999 by the American Chemical Society

Exaggerated stress-induced release of nonesterified fatty acids in JCR:LA-corpulent rats

Studies were performed to test the hypothesis that the stress response is exaggerated in obesity and to identify which component of the response is modified. Chronically cannulated lean (+/+) and obese ( cp cp ) JCR:LA rats were subjected to mild restraint stress for 15 minutes. Blood pressure and serum glucose, insulin, and corticosterone responses did not differ significantly between genotypes before, during, or after restraint. Lean rats had a significantly greater plasma epinephrine (EPI) response but a similar norepinephrine (NE) response compared with obese rats. Serum nonesterified fatty acid (NEFA) concentrations were unchanged in lean rats, but increased from 0.86 to a mean of 1.48 mmol/L in obese rats within 10 minutes of restraint. All animals recovered to prestress values by 45 minutes postrestraint. In obese rats, handling increased NEFAs to greater than 2 mmol/L before or at 165 minutes after restraint. In lean rats, NEFAs increased when handling occurred at 165 minutes after restraint, but there was no significant NEFA response at the prerestraint point. The sensitivity of adipose tissue to NE-induced lipolysis was not significantly different between genotypes. It is concluded that the exaggerated accumulation of NEFAs in the blood of obese rats results from increased adipose tissue mass. These increases in NEFAs in obese rats resulting from mild stress reached levels normally associated with gross pathology such as ketotic diabetes.

Adipocyte macrophage colony-stimulating factor is a mediator of adipose tissue growth.

Adipose tissue growth results from de novo adipocyte recruitment (hyperplasia) and increased size of preexisting adipocytes. Adipocyte hyperplasia accounts for the severalfold increase in adipose tissue mass that occurs throughout life, yet the mechanism of adipocyte hyperplasia is unknown. We studied the potential of macrophage colony-stimulating factor (MCSF) to mediate adipocyte hyperplasia because of the profound effects MCSF exerts on pluripotent cell recruitment and differentiation in other tissues. We found that MCSF mRNA and protein were expressed by human adipocytes and that adipocyte MCSF expression was upregulated in rapidly growing adipose tissue that encircled acutely inflamed bowel and in adipose tissue from humans gaining weight (4-7 kg) with overfeeding. Localized overexpression of adipocyte MCSF was then induced in rabbit subcutaneous adipose tissue in vivo using adenoviral-mediated gene transfer. Successful overexpression of MCSF was associated with 16-fold increases in adipose tissue growth compared with a control adenovirus expressing beta-galactosidase. This occurred in the absence of increased cell size and in the presence of increased nuclear staining for MIB-1, a marker of proliferation. We conclude that MCSF participates in adipocyte hyperplasia and the physiological regulation of adipose tissue growth.

Transgenic and knockout rodents: Novel insights into mechanisms of body weight regulation

Transgenic animals that over- or underexpress a protein of interest have been used to study obesity development, prevention, and susceptibility to diet-induced obesity such as a high-fat diet. Several transgenic models are resistant to diet-induced obesity including those that overexpress the insulin-sensitive glucose transporter, GLUT4, in adipose tissue only. In this animal there is increased adipose tissue mass but the animal maintains its insulin sensitivity. The overexpression of lipoprotein lipase (LPL) in skeletal muscle and the elimination of a protein kinase A subunit both resulted in lean and obesity resistant animals. By directing the production of the diphtheria toxin A chain to adipose tissue only the resulting animals not only had less adipose tissue mass but were resistant to MSG-induced obesity. Conversely, transgenic models with decreased brown adipose tissue or its function have all resulted in obese animals, highlighting the importance of thermoregulation in body weight maintenance. The use of transgenic technology in the field of obesity has emphasized the regional differences among fat pads as well as the dissimilarity between genders in fuel metabolism. Several transgenic models have separated obesity from insulin resistance allowing the importance of each state to be studied individually. Results using transgenic animals have re-emphasized that obesity is a polygenic disease.

Evidence that reduced leptin levels, but not an aberrant sequence of leptin or its receptor, contribute to the obesity syndrome in NON mice.

NON mice exhibit a polygenic syndrome of mild obesity which is less pronounced than that of the ob and db strains. Here, we have shown that the syndrome is accompanied by a rise in leptin mRNA levels in adipose tissue, corresponding with the increase in adipose tissue mass. Surprisingly, levels of the leptin protein in adipose tissue and serum were comparable to those of lean control animals (BL57/Ksj-+/+), and markedly lower than those in db/db-mice. The coding regions of the cDNA sequences of both leptin and the leptin receptor from NON mice were identical with those of the wild-type sequences. We suggested that low levels of leptin in adipose tissue and serum contribute to the obesity of NON mice.

Decline of plasma growth hormone binding protein in old age.

Aging is associated with a progressive decline in GH secretion and serum insulin-like growth factor (IGF)-I levels. This change in the GH-IGF axis is thought to contribute to the changes in body composition associated with aging, such as a loss in lean body mass and an increase in adipose tissue mass. Although the decrease in GH secretion starts in the third decade of life, marked changes in muscle mass and strength become apparent only much later. To assess whether a component of GH resistance supervenes in senescence, we studied plasma GH binding protein (GHBP) levels in 50 normal subjects between the ages of 61 and 98 yr. The GHBP is a soluble, circulating ectodomain of the GH receptor (GHR); its plasma level is thought to reflect GHR levels in tissues and, hence, GH responsivity. GHBP activity in plasma declined progressively between age 60 and 98 yr. The GHBP levels in nonagenarians was about half that of persons aged 60-65. This contrasts with younger adults, where GHBP levels remain relatively stable between the ages of 20 and 60. We conclude that in advanced age. GHBP and, by inference, GHR levels, decrease, which may add an element of GH resistance to the already compromised GH secretion status, thereby further contributing to the changes in body composition and frailty in the elderly.

Inherent Abnormalities of Fat Cells from Massively Obese Individuals.

In vitro investigations into adipose cell dynamics have revealed intrinsic characteristics of massively obese individuals' cells that could contribute to a relatively intractable expanded tat mass. Morbidly corpulent peoples' preadipocytes replicate to a greater degree than those from lean individuals. Coupled with exaggerated differentiation this enhanced growth would result in a greater number of tat cells which would increase adipose tissue mass. The relative resistance to de-differentiation that adipocytes from the massively obese demonstrate would contribute to stability of an increased number of adipocytes further exacerbating the problem. The increased message of an energy sensing protein, the obese gene product, suggests that the morbidly obese are insensitive to its action. Together these attributes provide a strong argument for a significant genetic role in the pathogenesis of obesity.

Persistence of metabolic consequences in the progeny of rats fed a HC formula in their early postnatal life

First-generation (1-) male and female rat pups were either reared artificially on a high-carbohydrate (HC) or a high-fat (HF) formula or nursed by mother (MF) from day 4 and weaned onto a stock diet on day 24. 1-HC rats compared with sex-matched control rats (1-HF and 1-MF) were hyperinsulinemic and mildly obese by day 60. We investigated the effect of maternal hyperinsulinemia on the second generation (2-) by intragroup breeding. The 2-HC male and female rats were hyperinsulinemic on day 45, had significantly increased growth rate from approximately day 60 onward, and became obese as evidenced by increased adipose tissue mass due to hypertrophy on day 100. The lipogenic capacity of liver and adipose tissues was significantly higher in the 2-HC than in control rats. Thus the metabolic changes that occurred in the first-generation rats fed a HC formula during early postnatal life not only persisted into their adult life but were also passed on to the next generation.

Left ventricular filling in young normotensive obese adults

Obesity is a condition of increased adipose tissue mass. The association between cardiovascular diseases and obesity are well documented. 1,2 An excess of body fat requires a high cardiac output to meet high metabolic demands. If this hemodynamic burden is sustained, cardiac adaptation may cause premature impairment of left ventricular (LV) contractile function. 3–5 No information is known about LV filling in normotensive young obese subjects. The present study analyzes the effect of obesity on LV dimension, wall thickness and diastolic filling in 30 healthy young obese subjects.

Targeted expression of a toxin gene to adipose tissue: transgenic mice resistant to obesity : Genes Dev. 7, 1318–1324

Obesity is characterized by increased adipose tissue mass and is often accompanied by a number of other disorders, such as diabetes, hypertension, and hyperlipidemia. To investigate the interrelationship between excessive adipose tissue mass and these associated disorders, we have attempted to reduce adiposity via targeted expression of an attenuated diphtheria toxin A chain to adipose tissue, using the 5' regulatory region of the adipocyte P2 (aP2) gene. Transgenic mice with high levels of toxin expression developed chylous ascites and died shortly after birth. Transgenic mice expressing lower levels of the transgene had normal adiposity and survived to adulthood; however, they showed a complete resistance to chemically induced obesity. Nevertheless, these animals developed hyperlipidemia equal to or greater than their nontransgenic obese littermates. Moreover, MSG-treated transgenic females were fertile, unlike their obese nontransgenic littermates. These data demonstrate the feasibility of gentle manipulation of adiposity and allow a functional dissection of obesity and its metabolic sequelae.

Targeted expression of a toxin gene to adipose tissue: transgenic mice resistant to obesity.

Obesity is characterized by increased adipose tissue mass and is often accompanied by a number of other disorders, such as diabetes, hypertension, and hyperlipidemia. To investigate the interrelationship between excessive adipose tissue mass and these associated disorders, we have attempted to reduce adiposity via targeted expression of an attenuated diphtheria toxin A chain to adipose tissue, using the 5' regulatory region of the adipocyte P2 (aP2) gene. Transgenic mice with high levels of toxin expression developed chylous ascites and died shortly after birth. Transgenic mice expressing lower levels of the transgene had normal adiposity and survived to adulthood; however, they showed a complete resistance to chemically induced obesity. Nevertheless, these animals developed hyperlipidemia equal to or greater than their nontransgenic obese littermates. Moreover, MSG-treated transgenic females were fertile, unlike their obese nontransgenic littermates. These data demonstrate the feasibility of gentle manipulation of adiposity and allow a functional dissection of obesity and its metabolic sequelae.

Central effects of monosodium glutamate on feeding behavior in adult long-evans rats

Monosodium glutamate (MSG) is known as a neurotoxic molecule when injected neonatally in rats, where it produces a marked decrease in food intake and an increase in adipose tissue mass. But, in adult rats subcutaneous injections of MSG produce a small, dose-dependent increase in food intake. It is not known if this action is centrally or systemically mediated. Therefore, the feeding pattern of adult rats injected intracerebroventricularly with MSG was measured. Seven days after installation of a cannula in the right lateral ventricle, rats were injected either with artificial cerebrospinal fluid or twice with 3 mg/brain MSG within a 3-day interval. The feeding pattern was recorded via a complete computerized system during 24 h. Feeding behavior was significantly modified by MSG treatments. These effects were observed immediately after drug injections, that is, upon the first meal, as well as during the 24 h that followed. For the first meal, modifications in meal size (+285%; p = 0.0001), meal duration (×10; p = 0.0005), postmeal interval (×4; p = 0.0005), and the satiety ratio (− 50%; p = 0.01) were observed. During the 24-h postinjection period, modifications in meal number (−3; p = 0.0007), total amount of food eaten (+21%; p = 0.007), time spent eating (+40%; p = 0.007), meal duration (+53%; p = 0.005), and meal size (+44%; p = 0.01) were noted. When the two MSG injections were compared, differences were also noted. For the first meal, postmeal interval (−50%; p < 0.005) and satiety ratio (−50%; p < 0.005) were decreased after the second injection. During the 24-h postinjection period, meal duration (−50%; p < 0.05) and time spent to eat (−25%; p < 0.05) were also decreased. This study showed that MSG must be considered a potent stimulant of food intake when administered through a central route. This effect was more powerful than that observed with systemic MSG injection, even at several thousand-fold smaller doses. This stimulation of food intake might be mediated by the stimulatory effect of MSG on release of neuromodulators present in the circumventricular nuclei such as the arcuate nucleus. A small neurotoxic action of MSG is possible when the injections are repeated.

Glycerol production in subcutaneous adipose tissue in lean and obese humans.

To estimate the regional subcutaneous glycerol production rate in normal and obese humans, the venous arterialized plasma glycerol, interstitial glycerol in the subcutaneous adipose tissue together with adipose tissue blood flow (ATBF, ml/100 g.min) were measured in the postabsorptive state and for 2 h after ingestion of 100 g of oral glucose. Eight lean and eight obese men with normal oral glucose tolerance tests were investigated with the subcutaneous microdialysis technique and 133Xe clearance. In the postabsorptive state, the interstitial glycerol concentrations in lean and obese subjects were 170 +/- 21 vs. 282 +/- 28 microM (P less than 0.01) and 156 +/- 23 vs. 225 +/- 12 microM (P less than 0.05) in the abdominal and femoral subcutaneous adipose tissue, respectively. The corresponding arterial glycerol levels were 54 +/- 4 vs. 75 +/- 14 microM (NS). Abdominal ATBF was greater in lean subjects (3.2 +/- 0.6 vs. 1.6 +/- 0.3; P less than 0.05), whereas femoral ATBF was similar in both groups (2.7 +/- 0.4 vs. 2.4 +/- 0.7). Estimated mean local glycerol release (mumol/100 g.min) was similar in the lean and obese group (0.16 +/- 0.03 vs. 0.20 +/- 0.05 and 0.18 +/- 0.02 vs. 0.17 +/- 0.04) in the abdominal and femoral site, respectively. We conclude that glycerol production from the subcutaneous tissue is increased in obesity, irrespective of adipose tissue distribution. This enhancement is due to the increased adipose tissue mass.

Kinetics of distribution and elimination of DDE in rats

1. Rats were given single i.v. doses of 14C-DDE, and total drug (14C) and unchanged DDE (g.l.c.) were measured for up to 14 days in blood, tissues, and excreta. The 14C recoveries amounted to 90.0 +/- 10.8 (SD) % dose. 2. DDE underwent redistribution from blood to liver, muscle, skin and, ultimately, adipose tissue. The tissue/blood concentration ratios were 6 for liver and muscle, 35 for skin, 400 for adipose tissue. Concentrations in blood and lean tissues declined biphasically with beta-half-lives of 8-12 days. The half-lives for adipose tissue and total body burden were larger by one order of magnitude. However, due to the increase of adipose tissue mass with time, the amount of DDE stored therein remained constant at almost 60% dose. 3. Except for liver, no substantial metabolite concentrations in tissues were found. In particular, lipophilic metabolites were clearly absent. Thus, tissue kinetics and storage are controlled by unchanged DDE. 4. Of a given dose of DDE, 31% was excreted in the faeces as polar metabolites within 14 days, and 3-4% dose as DDE. Urinary excretion was negligible. The beta-half-life of faecal excretion was equal to the one in blood and lean tissues. It is concluded that excretion is limited by the slow formation of polar metabolites of DDE.

Diagnosis and Prevalence of Obesity

Obesity is a condition of increased adipose tissue mass. Many techniques are available for measurement of body fat, but none is available widely for clinical purposes. The new technique of bioelectrical impedance may change this in the future. For now, relative weight and BMI are used as indices of obesity, which may be defined as a BMI greater than 30 kg per m2. This corresponds to a relative weight approximately 120 per cent above desirable. According to this definition, obesity exists in 10 to 12 per cent of adult men and women in the United States and Canada.

Total body water-to-lean body mass ratio in baboons (Papio sp.) of varying adiposity.

Total body water (TBW), lean body mass (LBM), and triglyceride mass were measured in 23 5-yr-old baboons (13 females and 10 males). Male baboons weighed more, had more LBM, more TBW, and contained less triglyceride mass per unit body weight than female baboons. Among all baboons, triglyceride mass per unit body weight ranged from 2.4 to 33.5%. The ratio TBW:LBM ranged from 0.70 to 0.92, increasing (r = 0.98) with increased body triglyceride content (both percent and absolute mass) in both male and female baboons. However, the water content per unit weight of tissues free of fat cells (liver, lungs, kidneys, central nervous system, eyes, tongue) was nearly constant at 0.73 +/- 0.02. The increase in TBW:LBM is more than can be expected from the water in the increased adipose tissue mass. We conclude that TBW:LBM is not constant but is influenced by body triglyceride content in baboons.

Anorexia after adrenalectomy in gold thioglucose-treated obese mice: Role of adipose tissue mass

We have previously shown that following adrenalectomy, gold thioglucose (GTG)-treated hyperphagic obese mice exhibit anorexia, weight loss and a pronounced hypoglycemia which leads ultimately to their death. In the present study, we sought to determine whether the increased adipose tissue mass which is characteristic of GTG-treated obese mice exerted a role in the onset and development of anorexia after adrenalectomy. Accordingly, the effects of adrenalectomy on food intake, weight gain, plasma glucose and corticosterone levels were investigated in normal untreated controls, GTG-treated hyperphagic obese mice and GTG-treated non obese mice. The GTG-treated non obese mice were prepared by restricting their daily intake of chow (pair-feeding) to that consumed by normal untreated mice. After adrenalectomy, all mice were allowed free access to food. As expected, all GTG-treated hyperphagic obese mice exhibited anorexia and weight loss following adrenalectomy. In contrast, about half (52%) of the GTG-treated non obese mice exhibited anorexia and weight loss after adrenalectomy. The response of the GTG-treated non obese adrenalectomized mice was not due to differences in adrenal insufficiency since all adrenalectomized mice had blood levels of corticosterone of less than 0.5 μg%. These findings indicate that whereas the increased adipose tissue mass of the GTG-treated obese mice appears to be associated with an increased incidence of anorexia following adrenalectomy, increased adipose tissue mass alone does not appear to be essential for the occurrence of anorexia.

Enhanced conversion of androstenedione to estrogens in obese males.

In normal and obese young males [90--120% and > 160% of ideal body weight (IBW); IBW = 100%], plasma concentrations of testosterone, androstenedione, estrone, and estradiol were measured. Metabolic clearance and production rates of androstenedione and the conversion ratios of androstenedione to testosterone, estrone, and estradiol were determined using the constant infusion technique. In the obese subjects, IBW was inversely correlated (P < 0.001) with plasma concentrations of androstenedione (r = 0.81) and testosterone (r = 0.87), while the levels of estrone (r = 0.92) and estradiol (r = 0.95) increased with IBW (P < 0.001). Thus, when normal and obese subjects were compared as groups, plasma androstenedione decreased form 1.24 +/- 0.13 to 0.93 +/- 0.15 ng/ml (mean +/- SD) and plasma testosterone decreased from 5.89 +/- 0.82 to 3.29 +/- 0.92 ng/ml (P < 0.001), while estrone increased from 28.2 +/- 3.4 to 60.0 +/- 9.4 pg/ml, and estradiol increased from 21.7 +/- 3.5 to 43.9 +/- 5.3 pg/ml. The testosterone to androstenedione and the estradiol to estrone ratios were not different in obesity, but changes in IBW were positively correlated (P < 0.001) with differences in the estrone to androstenedione (r = 0.93) and estradiol to testosterone ratios (r = 0.93), indicating that fat tissue may aromatize androgens, whereas reduction of 17-oxo-steroid appears to be of minor importance. As the MCR of androstenedione increased with IBW (from 2156 to 2636 liters/day P < 0.05) while plasma levels decreased, the apparent production rate of androstenedione was not influenced by the degree of obesity. The conversion of androstenedione to estrone (r = 0.89) and of androstenedione to estradiol (r = 0.82) was enhanced in obese subjects (P < 0.001). We suggest that enhanced aromatization of androstenedione due to an increased adipose tissue mass may account for the high plasma estrogen levels observed in obese men.

The cellularity of ovine adipose tissue

The cellular growth of adipose tissue from Dorset Horn x Merino wethers was characterized by both hypertrophy and hyperplasia of adipose cells until the sheep were c. 11 months old, after which hypertrophy of existing adipose cells was solely responsible for increases in adipose tissue mass. Omental adipose tissue contained larger adipose cells than either the perirenal or subcutaneous sites. The weight of fat which had been deposited in the boneless carcass meat and the internal adipose tissue depots were linearly and positively correlated with the volume of the adipose cells. Decreases in the mass of adipose tissue, which accompanied nutritional restriction, were due to decreased adipose cell size, since no change was observed in the number of adipose cells per carcass after loss in weight. The cellularity characteristics of rehabilitated sheep were similar to those of sheep which had undergone continuous growth.