Effects of Exogenous Recombinant Human Growth Hormone on an Animal Model of Suboptimal Nutrition

Background: Nutritional dwarfing, a form of suboptimal nutrition, has been identified as a frequent cause of short stature and delayed sexual development in children. Retarded growth is an adaptive response to suboptimal nutrition.

Objective: To assess whether recombinant human growth hormone (rhGH) may promote growth during various levels of suboptimal nutrition.

Methods: Using a previously developed rat model of suboptimal nutrition, six groups of rats (six rats/group) were fed a balanced 1:1 carbohydrate:fat ratio diet for 4 weeks. Three of the groups were administered daily injections of rhGH (0.1 mg/100 g BW) subcutaneously in the back while the other three groups were kept as controls and were given similar dosages of normal saline solution (NSS). Restricted rats within each treatment group were pair fed 80 and 60% of the ad-libitum rats intake. Daily intake of the 80 and 60% fed groups were determined based on the intake of the ad-libitum fed groups. Serum IGF-I and insulin were determined after 4 weeks of dietary treatment by radioimmunoassay while IGFBP-3 was determined by an immunoradiometric assay. Body composition was assessed in all rats by carcass analysis.

Results: After 4 weeks, total weight gain and tail growth were higher (p<0.05) in the rhGH treated group at 80 and 60% of-libitum energy intake. Serum levels of IGF-I and IGFBP-3 were higher (p<0.05) in rhGH treated rats fed at 60% of ad-libitum. In comparison to the NSS groups, administration of rhGH in rats fed ad-libitum increased total body water. Energy restriction caused decreased fat percentage (p<0.05) in both rhGH and NSS groups without differences among treated groups.

Conclusion: These results suggest that the anabolic effects of rhGH may overcome mild to moderate energy restriction.     

Growth deceleration and bone metabolism in nutritional dwarfing rats

Nutritional status as well as energy and protein intake are critical regulators of IGF-1 and IGFBP-3 and contribute to the modulation of bone remodeling and formation. The purpose of this study was to investigate on an experimental model with nutritional dwarfing (ND), whether the alterations on body growth velocity, energy metabolism and body composition could affect serum concentrations of IGF-1 and IGFBP-3 and bone (tibiae and mandible) histology and histomorphometry. Twenty-one male weanling Wistar rats (body weight = 38.20 +/- 0.94 g) were randomized to three groups: seven of them were killed at day = 0 (CO, n = 7); control (C, n = 7); and experimental 80 (E80, n = 7). During 4 weeks, C was fed ad libitum with a 1:1 carbohydrate to fat diet. E80 was being underfed with the same diet by 80% and the following parameters were measured: weight (Wt) for length (L) ratio z-score; oxygen consumption (VO2); body composition (BC) by EM-SCAN SA 3000. At t = 28, E80 and C were killed. Serum IGF-1 and IGFBP-3 and bone histology and histomorphometry were performed on C0, E80 and C. E80 showed Wt for L z-score between lean and adequate, a decrease in VO2 according to body proportions, a BC of a delayed puberty individual, IGF-1 and IGFBP-3 decreased by 56 and 53%, respectively. Tibiae's hematopoyetic and adipose bone marrow areas were combined, with sealing trabeculae on metaphyseal areas. This study suggests that there is a relationship among growth deceleration in ND rats and structural alterations on tibiae.     

Growth deceleration and bone metabolism in nutritional dwarfing rats

Nutritional status as well as energy and protein intake are critical regulators of IGF1 and IGFBP-3 and contribute to the modulation of bone remodeling and formation. The purpose of this study was to investigate on an experimental model with nutritional dwarfing (ND), whether the alterations on body growth velocity, energy metabolism and body composition could affect serum concentrations of IGF-1 and IGFBP-3 and bone (tibiae and mandible) histology and histomorphometry. Twentyone male weanling Wistar rats (body weight = 38.20 ± 0.94 g) were randomized to three groups: seven of them were killed at day = 0 (CO, n = 7); control (C, n = 7); and experimental 80 (E80, n = 7). During 4 weeks, C was fed ad libitum with a 1: 1 carbohydrate to fat diet. E80 was being underfed with the same diet by 80% and the following parameters were measured: weight (Wt) for length (L) ratio z-score; oxygen consumption (VO 2); body composition (BC) by EM-SCAN SA 3000. At t = 28, E80 and C were killed. Serum IGF-1 and IGFBP-3 and bone histology and histomorphometry were performed on C0, E80 and C. E80 showed Wt for L z-score between lean and adequate, a decrease in VO 2 according to body proportions, a BC of a delayed puberty individual, IGF-1 and IGFBP-3 decreased by 56 and 53%, respectively. Tibiae's hematopoyetic and adipose bone marrow areas were combined, with sealing trabeculae on metaphyseal areas. This study suggests that there is a relationship among growth deceleration in ND rats and structural alterations on tibiae.     

添加rhGH与Gln的肠外营养对短肠大鼠代谢效应的影响

目的研究添加人重组生长激素(rhGH)及谷氨酰胺(Gln)的肠外营养(PN)对短肠大鼠机体合成代谢的作用及作用机制. 方法将SD大鼠按2×2析因设计方案随机分成STD、Gln、rhGH及GG 4组,建立PN短肠大鼠动物模型.测定各组大鼠体重及氮平衡变化,测定PN后大鼠各组织器官重量及机体总体水、脂肪及蛋白含量变化,测定血GH及IGF-1浓度. 结果 rhGH组及GG组大鼠体重显著增加,氮平衡改善;腓肠肌重量增加;机体总体蛋白明显升高,体脂下降;血GH及IGF-1显著升高,P值均<0.05;单位长度小肠重量在Gln与rhGH组显著增加,GG组增加最为明显,P<0.05. 结论 rhGH具有显著的促机体合成代谢作用,Gln作用不明显,但二者对残余小肠代偿具有协同促进作用.IGF-1在rhGH的促合成代谢机制中起重要介导作用.     

Exogenous recombinant human growth hormone effects during suboptimal energy and zinc intake

BACKGROUND: Energy and Zinc (Zn) deficiencies have been associated with nutritional related growth retardation as well as growth hormone (GH) resistance. In this study, the relationship between suboptimal energy and/or Zn intake and growth in rats and their response to immunoreactive exogenous recombinant human GH (GHi), was determined. RESULTS: Rats treated with GHi and fed ad-libitum energy and Zn (100/100) had increased IGFBP-3 (p < 0.05) as compared with NSS (215 +/- 23 vs. 185 +/- 17 ng/ml) along with similar body weight gain. Rats treated with GHi and fed suboptimal energy and full Zn (70/100) had significantly increased weight gain (109.0 +/- 18.2 vs. 73.8 +/- 11.0 g) and serum IGF-I levels (568 +/- 90 vs. 420 +/- 85 ng/ml), along with decreased total body water (TBW; 61.0 +/- 1.6 vs. 65.7 +/- 2.1%) as compared to NSS controls. However, body weight gain was reduced (p < 0.05) as compared with rats fed ad-libitum energy. Growth hormone treated rats fed only suboptimal Zn (100/70), had increased weight gain (217.5 +/- 13.2 vs. 191.6 +/- 17.9 g; p < 0.05) compared to those given NSS. These rats gained weight in similar amounts to those fed full Zn. Rats treated with GHi and fed both suboptimal energy and Zn (70/70) showed similar results to those fed suboptimal energy with appropriate Zn (70/100), along with significant increases in IGFBP-3 levels (322 +/- 28 vs. 93 +/- 28 ng/ml). All restricted rats had reduced 24-h EE (kcal/100 g BW) and physical activity index (oscillations/min/kg BW) and GHi did not overcome these effects. CONCLUSION: These results suggest that GHi enhances weight gain in rats with suboptimal energy and Zn intake but does not modify energy expenditure or physical activity index. Suboptimal Zn intake did not exacerbate the reduced growth or decrease in energy expenditure observed with energy restriction.     

Severe feed restriction of pregnant swine and rats: effects on postweaning growth and body composition of progeny

Rats and swine were restricted in feed during pregnancy to determine the effect on postnatal growth and development of the progeny. Restriction of rats to 50% of preconception feed intake during the first 2 wk of gestation was associated with higher body weight of the progeny at 21 wk postpartum than was ad libitum feeding throughout gestation. However, maternal intake during gestation had no effect on perirenal and gonadal fat weight or adipocyte size in male and female offspring at 160 d of age. Restriction of swine to one-third of recommended feed intake during the first 10 wk of pregnancy was associated in the progeny with less perirenal and subcutaneous backfat and smaller adipocytes in depot fat compared with progeny of adequately fed swine. It is concluded that feed restriction of pregnant rats to one-half of preconception intake for the first two-thirds of pregnancy results in increased weight gain in the resulting progeny while restriction of swine to one-third of the recommended feed allowance during the first two-thirds of pregnancy results in reduced postweaning weight gain and decreased fat accretion during young adulthood.     

Effect of sera from control and overfed rats on preadipocyte growth in culture

Increased body lipid was induced in 4-wk-old rats through oral gavage. Rats were either fed ad libitum, tube-fed 100% or tube-fed 150% of the ad libitum intake. After 1 wk of tube-feeding animals were killed and sera collected. Sera were used to support the growth of rat stromal-vascular cells in culture. Sera were also analyzed for growth hormone and insulin concentrations. In rats that were tube-fed, levels of adiposity were greater but sera from these rats decreased stromal-vascular and preadipocyte proliferation in culture when compared with sera from ad libitum-fed rats. Sera from tube-fed animals promoted an increase in preadipocyte differentiation as revealed by esterase staining. Results indicate that overfeeding in juvenile rats causes sera changes that support fat cell differentiation but not fat cell hyperplasia.     

Hydroxycitrate has long-term effects on feeding behavior,body weight regain and metabolism after body weight loss in male rats

We examined the long-term effect of hydroxycitrate (HCA) on food intake, meal patterns, body weight regain and energy conversion ratio as well as on different blood and liver variables in rats after substantial body weight loss. Rats were fed a 1% (g/100 g) fat diet (81% carbohydrate, 10% protein, 1% fat) or a 12% (g/100 g) fat diet (76% carbohydrate, 9% protein, 12% fat) in two separate experiments. Supplementing both diets with 3% HCA after 10 d of restrictive feeding reduced body weight regain over the whole subsequent period of ad libitum consumption (22 d) and decreased the energy conversion ratio [body weight regain (g)/energy intake (MJ)] at the end of the experiment. Only in rats fed the 12% fat diet, HCA had a long-term suppression of food intake. The anorectic effect occurred predominately during the light phase, and was due mainly to a reduction in numbers of meals. In rats fed the 12% fat diet, HCA had no effect on plasma beta-hydroxybutyrate (BHB), but reduced plasma triacylglycerol and increased liver fat concentration. In rats fed the 1% fat diet, HCA did not affect any metabolic variable examined. Thus, the suppressive effect of HCA on body weight regain, which was maintained for at least 3 wk, appears to be independent of the dietary fat content. Yet, the fat content of the diet seemed to be important for the long-term suppressive effect of HCA on feeding. The fact that HCA did not change plasma BHB concentration does not support a role for increased hepatic fatty acid oxidation in the anorectic effect of HCA.     

Influence of selected amino acid deficiencies on somatomedin, growth and glycosaminoglycan metabolism in weanling rats

The effects of lysine-, methionine- or histidine-deficient diets compared to a control diet fed ad libitum or 15, 10 or 5 g/d were studied in weanling rats. Feed intake was 5-7 g/d for the amino acid-deficient animals. After 3 wk, all amino acid-deficient rats had lost more weight (P less than 0.01) than the controls fed at comparable energy levels. Serum somatomedin (Sm) activity was significantly decreased in lysine- (0.55 U/ml), methionine- (0.32 U/ml) and histidine-deficient (0.38 U/ml) rats compared to rats fed the control diet ad libitum (1.6 U/ml). Differences between amino acid-deficient and calorie-restricted animals were not significant. A similar response was observed in 35SO4 uptake by cartilage glycosaminoglycans (GAG). Caloric restriction and amino acid deficiency each resulted in lower 35SO4 uptake by cartilage GAG than occurred with ad libitum feeding, but there were no significant differences between the rats fed amino acid-deficient diets and those fed 5 or 10 g of the control diet. Compared to rats fed the control diet ad libitum, plasma growth hormone (GH) concentrations were lower in the rats fed 5 or 10 g of control diet per day and in those fed amino acid-deficient diets (P less than 0.05), but GH concentrations were not consistent with the growth retardation observed. The results confirm that Sm and GAG activities are reduced in protein-energy restriction independent of GH. However, changes could not be attributed to specific deficiencies of lysine, methionine and/or histidine.     

Effects of structured medium- and long-chain triacylglycerols in diets with various levels of fat on body fat accumulation in rats

The effects of structured medium- and long-chain triacylglycerols (MLCT) in diets containing 50-200 g fat/kg on body fat accumulation were compared with those of long-chain triacylglycerols (LCT) in rats. In rats fed ad libitum, weights of intra-abdominal adipose tissues and carcass fat contents were significantly smaller (P<0.05) in rats fed the 150-200 g MLCT/kg diet than in rats fed 150-200 g LCT/kg diet. Serum and liver triacylglycerol contents were significantly greater (P<0.05) in rats fed 200 g MLCT/kg diet, as were hepatic capacities of citrate synthase and cytochrome oxidase (P<0.05). The effects of MLCT on body fat were also examined in adult rats fed a limited amount of food (approximately 50 % of ad libitum intake). Reduction of body fat deposition during the food restriction was the same between in LCT and MLCT groups. These results suggest that accumulation of body fat was less efficient during long-term feeding of MLCT than LCT in rats fed high-fat diets ad libitum. The effect of MLCT on body fat might be influenced by the dietary fat content or by energy sufficiency.     

Influence of diet on growth in the rat

Twenty-eight-day old male Sprague Dawley rats were fed, either ad libitum or in restricted amounts, isoenergetic diets containing 2%, 5%, 10%, 15%, 25%, or 50% lactalbumin protein and 5%, 11.9%, or 21.1% fat for 8 weeks and were then killed. Weekly food consumption and body weight, terminal weight, body water and lipid, and liver weight, DNA, RNA, protein, and lipid were measured. The growth rate increased progressively with each increase in the level of dietary protein up to 25% protein and then declined. Growth was also accelerated by a high fat diet but was retarded by restriction of energy intake. Total body lipid correlated directly with the level of fat in the diet. Multiple regression analysis of the type: Y = beta0 + beta1X1 + beta2X2 + B3X3 + B4X4 where Y = rate of weight gain X1 = dietary protein level, X2 = protein efficiency ratio, X3 = appetite factor, and X4 = energy/protein ratio, showed that the maximum rate of weight gain of 58.8 g/week occurred when the diet contained 23% protein. Growth rate declined when the diet contained a higher protein level.     

Effect of selenium on rat growth, growth hormone and diet utilization.

Female rats were fed a selenium-deficient diet composed of Torula yeast, sucrose, vitamins (including tocopheryl acetate) and minerals from weaning and during breeding, gestation and lactation. The offspring were used to study the effects of selenium on growth, diet utilization and growth hormon status. The Torula yeast diet containing 200 IU dl-alpha-tocopheryl acetate was fed alone or supplemented with 0.025 or 0.1 ppm of selenium as selenite. Rats fed the selenium-supplemented diets grew significently faster and consumed significantly more diet than rats fed the unsupplemented diet. Anterior pituitary weights were lower in selenium-deficient rats, but if expressed per unit of body weight, were similar to pituitary weight of selenium-supplemented animals. Total growth hormone in the anterior pituitary was reduced in selenium-deficient rats. A metabolism study indicated that rats allowed ad libitum access to supplemented diets consumed more diet and obtained more metabolizable energy from the diet than rats fed the deficient diet. It the intake of rats fed the supplemented diets was limited to that of rats allowed ad libitum access to deficient diet, growth of rats was similar. However, metabolizable energy content of the diet increased quadratically and nitrogen digestibility increased linearly as thelevel of selenium increased. Selenium deficiency reduced growth primarily by decreased diet consumption, but also reduced the utilization of energy and nitrogen.     

Metabolic status in growing rats fed isocaloric diets with increased carbohydrate-to-fat ratio

OBJECTIVE: A low-fat diet is hypothesized to be associated with significant weight loss. However, most previous studies have been limited to low-fat, low-calorie restrictive diets. This study evaluated the effect of isocaloric diets given "ad libitum" but different in relative amounts of fat and carbohydrate on body size, energy metabolism, body composition, insulin-like growth factor-1, and leptin serum levels in growing Wistar rats. METHODS: Weanling male rats were fed with one of three diets that contained a ratio of carbohydrate to fat of 1:1, 2:1, or 3:1. Food intake, body weight, body length, oxygen consumption, and body composition were measured at ages 21 to 50 d. Serum levels of insulin-like growth factor-1 and leptin were also determined. RESULTS: Energy intake was similar across groups. The ratio of body weight to body length remained adequate throughout the experimental period. However, groups that received 3:1 and 2:1 showed increased weight and progressive decreases in energy expenditure, body fat composition, and serum level of leptin, but the ratio of insulin-like growth factor-1 to body length was not affected. CONCLUSIONS: Dietary substitution of fat with carbohydrates contributes to weight gain by decreasing energy expenditure and possibly by decreasing leptin secretion.     

Effects of dietary protein, fat and restriction on body composition and energy balance in lactating rats

Isoenergetic diets formulated at three levels of dietary protein using 12,24 and 40% casein and at two levels of fat using 2.26 and 13.82% corn oil were fed at five levels of intake, ad libitum, 75, 62.5, 50 and 37.5% of average ad libitum intake, to 90 lactating rats from d 7 to 14 of lactation. Regression equations developed from lactating rats killed on d 7 of lactation were used to calculate initial body composition and energy of rats killed on d 14 of lactation. Changes in body weight and body water were significantly (P less than 0.05) affected by dietary fat and protein, but change in dry lean body mass was affected only by level of dietary fat, whereas body nitrogen and fat and lean body energy were not affected by level of dietary fat or protein. However, restricted intake significantly increased loss of all these. Likewise, restricted intake decreased milk production. Changes in weights of heart and liver were not affected by diet or intake, whereas intestinal weight decreased with intake restriction. Liver enzyme activities were markedly affected by intake restriction, whereas responses to dietary protein and fat were marginal.     

赤霉素对雌性大鼠早期生长发育及胰岛素样生长因子表达水平的影响

目的探讨植物生长调节剂赤霉素对雌性SD大鼠生长发育及胰岛素样生长因子(IGF-1)表达水平的影响。方法选择刚断乳雌性SD大鼠40只,随机分为4组,即对照组,低、中、高赤霉素剂量组,分别按照0、2、100和200mg/kg赤霉素剂量经口灌胃,连续15天,每天记录身长、体重、阴道开口情况。染毒结束,剖杀受试动物,获得肝脏、卵巢、子宫,计算脏器系数。提取肝组织RNA进行RT-PCR,检测肝内IGF-1、胰岛素样生长因子捆绑蛋白(IGFBP-1)基因的表达水平。结果各组间大鼠的身长、体重,阴道开口时间,子宫、卵巢的脏器系数差异无显著性(P>0.05),肝组织内IGF-1、IGFBP-1平均表达水平差异亦无显著性(P>0.05),但高剂量组部分样本出现IGF-1、IGFBP-1表达强度倒置的现象。高剂量组动物的肝脏系数小于对照组(P<0.05)。结论在0～200mg/kg剂量范围赤霉素接触对雌性SD大鼠生长发育、肝脏内IGF-1及其捆绑蛋白的表达影响不明显,但200mg/kg剂量的赤霉素摄入可能对其肝脏产生损伤。     

Dietary soy and fats in relation to serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels in premenopausal Japanese women

Circulating levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) have each been associated with premenopausal breast cancer risks. We analyzed data from a cross-sectional study of 261 premenopausal Japanese women aged 20-54 yr with adequate nutritional status to evaluate the relationships between concentrations of IGF-1 and IGFBP-3 in serum and dietary intakes of soy, fats and other nutrients. Diet was assessed by a semiquantitative food frequency questionnaire. There was no significant correlation between soy product as well as soy isoflavone intake and serum IGF-1 or IGFBP-3 levels after controlling for age, total energy, percent body fat, and education level. Total fat intake was significantly inversely correlated with serum IGFBP-3 level (r = -0.13, P = 0.04). The correlations of saturated and monounsaturated fats with serum IGFBP-3 were of borderline significance (r = -0.12, P = 0.06 and r = -0.11, P = 0.07, respectively).     

A controlled high-fat diet induces an obese syndrome in rats

The prevalence of obesity is increasing. Although the etiology of obesity is complex, dietary factors, particularly the consumption of a high-fat (HF) diet, is considered a risk factor for its development. Nonetheless, a causal role of dietary fat has never been definitively documented, in part because of inadequate animal models. We developed a rat model of diet-induced obesity that will be a powerful tool for assessment of this issue. In four experiments, Long-Evans rats ate ad libitum a synthetic semipurified diet containing 20 g (HF) or 4 g [low-fat (LF)] of fat/100 g of diet or a nonpurified diet. Other rats ate ad libitum the HF diet in amounts matched to the energy intake of the LF rats. When compared over 10 wk of free feeding, HF rats weighed 10% more (P < 0.01) than LF rats and had 50% more body fat (P < 0.01), as well as significant hyperleptinemia and insulin resistance. Compared with rats fed the nonpurified diet, the HF rats had even more marked differences in these variables. The rats fed the HF diet to match the rats fed the LF diet had similar body weights but significantly more adipose tissue than LF rats, suggesting that diet composition and/or energy density of the diet affects fat deposition. This dietary regimen has reproducible effects on body size and composition, and these are similar in male and female rats. This model of diet-induced obesity will be a useful tool for studying the mechanisms by which dietary fat influences the regulation of energy balance.     

Effects of dietary protein, fat and energy intake during an initiation phase study of 7,12-dimethylbenz[a]anthracene-induced breast cancer in rats

A factorial experiment was conducted to examine the effects of dietary protein (8, 16, 32% of energy from casein) and dietary fat (12, 24, 48% of energy from corn oil) on the initiation of 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast carcinogenesis in rats. Forty weanling female Sprague-Dawley rats were assigned to each of nine diets fed ad libitum. After 4 wk each rat received DMBA (20 mg/kg) via gastric intubation. For an additional 22 wk after carcinogen administration all rats consumed a diet containing 16% of dietary energy from protein and 24% from fat. Dietary fat, protein and ad libitum energy consumption exhibited statistically significant effects on final tumor prevalence, but interactive effects were not found. At necropsy, rats fed corn oil at 12, 24 and 48% of energy prior to DMBA administration showed tumor prevalences of 58, 58 and 85% with 116, 153 and 231 total tumors, respectively. The data indicate a significant nonlinear effect of dietary fat. Corresponding numbers for rats fed casein at 8, 16 and 32% of energy prior to DMBA were prevalences of 79, 65 and 59%, with total tumor counts of 194, 144 and 162. Higher dietary protein during the initiation phase was associated with a significant reduction in tumor prevalence, which was most striking between 8 and 16% of energy from protein. In addition, results of multiple logistic regression showed that tumorigenesis was increased with greater ad libitum energy intake. The odds of a tumor at necropsy were multiplied by 1.19 for each kilocalorie increase in ad libitum energy intake averaged over the post-DMBA phase of the experiment. An additional six weanling rats fed each diet for 4 wk were killed for assay of hepatic carcinogen metabolizing enzymes at the time corresponding to DMBA administration in the initiation experiment. Both protein and fat showed independent effects on the activity of several enzymes. However, enzyme activity did not suggest a unifying mechanism whereby these nutrients influence DMBA-induced mammary carcinogenesis.     

Dynamic and static phases of severe dietary obesity in sheep: food intakes, endocrinology and carcass and organ chemical composition.

The chronology of changes in body weights, food intakes and plasma concentrations of selected metabolic hormones and metabolites were determined in sheep during the induction (dynamic) and static phases of diet-induced obesity. Lean adult Dorset ewes weighing 47 kg were fed a pelleted hay-grain diet at maintenance (lean; n = 7) or were fed the same diet ad libitum to a maximum intake of 3 kg.sheep-1.d-1 (obese; n = 8) for 78 wk. Body weight of obese sheep doubled (97 vs. 47 kg) by wk 42 of ad libitum intake. Average daily intakes of dry matter (12.8 g/kg) and digestible energy (165 kJ/kg) were comparable in maintenance-fed lean sheep and ad libitum-fed obese sheep consuming maintenance after wk 50, which began the static phase of obesity. Fasting plasma concentrations of insulin in the obese sheep increased steadily from 50 +/- 6 pmol/L at wk 0 to a sustained plateau of 249 +/- 21 pmol/L after wk 30. Plasma levels of glucose, immunoreactive glucagon and thyroid hormones were consistently greater (P less than 0.05) in obese sheep than in lean sheep after wk 2, 3 and 25, respectively, of the experiment. Concentration of lipid (49 vs. 25%) in the carcass stripped of internal fat was greater (P less than 0.01) in obese sheep than in lean sheep, but concentration of protein (10.4 vs. 15.3%) was less in the heavier carcass (58 vs. 24 kg) of the obese sheep. We conclude that hyperinsulinemia and abnormal fuel metabolism are early events during dynamic obesity and these defects persist throughout the static phase of obesity. Maintenance energy requirements relative to unit body weight (W1.0) seem similar in lean and dietary obese sheep.     

Effect of hydroxycitrate on respiratory quotient, energy expenditure, and glucose tolerance in male rats after a period of restrictive feeding

OBJECTIVE: Recently we demonstrated that hydroxycitrate (HCA) suppresses food intake and body weight regain in male rats after substantial body weight loss. However, it is not known whether HCA also affects the respiration quotient (RQ), energy expenditure (EE), and glucose tolerance in this animal model. METHODS: Twenty-four male rats (initial body weight, 378 +/- 3 g) were fed restrictively (10 g/d) for 10 d and then given ad libitum access to a high-glucose diet supplemented with 3% HCA for 6 d. Controls received the same diet without the supplement. RQ and EE were measured during ad libitum days 1, 2, and 6. An oral glucose tolerance test was performed on ad libitum day 4 or 5. RESULTS: HCA decreased RQ and EE during ad libitum days 1 and 2. In all probability, these findings reflect a decrease in de novo lipogenesis. On ad libitum day 6, RQ and EE did not differ between treatment groups. HCA suppressed food intake during the first 3 d ad libitum, but overall body weight regain was not decreased in the HCA group. The oral glucose tolerance test showed that HCA significantly decreased the increase in plasma glucose from baseline (Deltaglucose) and tended to decrease the area under the curve for glucose. Deltainsulin and area under the curve for insulin did not differ between groups. CONCLUSIONS: These results indicate that, in this animal model, HCA suppresses de novo lipogenesis. Moreover, HCA may improve glucose tolerance.