Epididymal Fat Pad Weight Research Articles

Desaturation indices in liver, muscle, and bone of growing male and female mice fed trans‐10, cis‐12 conjugated linoleic acid

trans-10,cis-12-CLA (t10,c12-CLA) inhibits lipid deposition in adipose tissue of many species, but it also enhances lipid deposition in liver. We evaluated effects of dietary t10,c12-CLA content and gender on carcass composition, FA profile of selected tissues, and expression of FA synthase (FAS) and stearoyl-CoA desaturase-1 (SCD) mRNA in adipose tissue. Male and female (63 of each) CD-1 mice were assigned a diet containing 0.0, 0.15, or 0.30% t10,c12-CLA at 4 wk of age. Seven mice per dietary group within gender were sacrificed after 2, 4, or 6 wk. The CLA isomer caused dose-dependent reductions in dry carcass weight and fat content, without altering protein content, but carcass fat and epididymal fat pad weights of males were reduced to a greater extent than carcass fat and inguinal fat pad weights of females. FAS and SCD mRNA in adipose tissue was more abundant in females than males, but expression in both genders decreased as the t10,c12-CLA content of the diet increased. Although the weight of gastrocnemius muscle was not influenced by diet, total FA content of the muscle of both genders decreased in response to dietary t10,c12-CLA content. Femur weight of male mice increased as the t10,c12-CLA content of the diet increased, but the weight increase was associated with a reduction in total FA content. The delta 9 desaturation indices for muscle and femur suggested a linear reduction in SCD activity, whereas delta 9 indices for liver indicated linear enhancement of SCD activity. Overall, results suggested that growing male mice were more susceptible than females to t10,c12-CLA inhibition of lipid deposition.

Swim training applied at early age is critical to adrenal medulla catecholamine content and to attenuate monosodium l-glutamate-obesity onset in mice

Exercise has been recommended as a remedy against a worldwide obesity epidemic; however, the onset of excessive weight gain is not fully understood, nor are the effects of exercise on body weight control. Activity deficits of the sympathetic nervous system, including the sympathoadrenal axis, have been suggested to contribute to high fat accumulation in obesity. In the present work, swim training was used to observe fat accumulation and adrenal catecholamine stocks in hypothalamic-obese mice produced by neonatal treatment with monosodium l-glutamate (MSG). MSG-treated and normal mice swam for 15 min/day, 3 days a week, from weaning up to 90 days old (EXE 21–90); from weaning up to 50 days old (EXE 21–50) and from 60 up to 90 days old (EXE 60–90). Sedentary MSG and normal mice (SED groups) did not exercise at all. Animals were sacrificed at 90 days of age. MSG treatment induced obesity, demonstrated by a 43.08% increase in epididymal fat pad weight; these adult obese mice presented 27.7% less catecholamine stocks in their adrenal glands than untreated mice ( p < 0.001). Exercise reduced fat accumulation and increased adrenal catecholamine content in EXE 21–90 groups. These effects were more pronounced in MSG-mice than in normal ones. Halting the exercise (EXE 21–50 groups) still changed fat accretion and catecholamine stocks; however, no effects were recorded in the EXE 60–90 groups. We conclude that metabolic changes imposed by early exercise, leading to an attenuation of MSG-hypothalamic obesity onset, are at least in part due to sympathoadrenal activity modulation.

PYY(3–36) reduces food intake and body weight and improves insulin sensitivity in rodent models of diet-induced obesity

The gut hormone peptide YY (PYY) was recently proposed to comprise an endogenous satiety factor. We have studied acute anorectic functions of PYY(3-36) in mice and rats, as well as metabolic effects of chronic PYY(3-36) administration to diet-induced obese (DIO) mice and rats. A single intraperitoneal injection of PYY(3-36) inhibited food intake in mice, but not in rats. We next investigated the effects of increasing doses (100, 300, and 1,000 microg.kg-1.day-1) of PYY(3-36) administered subcutaneously via osmotic minipumps on food intake and body weight in DIO C57BL/6J mice. Whereas only the highest dose (1,000 microg.kg-1.day-1) of PYY(3-36) significantly reduced food intake over the first 3 days, body weight gain was dose dependently reduced, and on day 28 the group treated with 1,000 microg.kg-1.day-1 PYY(3-36) weighed approximately 10% less than the vehicle-treated group. Mesenteric, epididymal, retroperitoneal, and inguinal fat pad weight was dose dependently reduced. Subcutaneous administration of PYY(3-36) (250 and 1,000 microg.kg-1.day-1) for 28 days reduced body weight and improved glycemic control in glucose-intolerant DIO rats. Neither 250 nor 1,000 microg/kg PYY(3-36) elicited a conditioned taste aversion in male rats.

고지혈증 흰쥐에 청국장 및 상황버섯 청국장이 지질대사에 미치는 효과

청국장 분말이 고지방식이를 섭취한 흰쥐의 지질대사에 미치는 영향을 조사하고자, 성숙한(생후 20주령) 숫쥐를 4주간 고지방식이(0.5% 콜레스테롤, 10% 지방)로 고지혈증을 유도한 후 대조군(고지방식이), 청국장군(고지방식이에 단백질원으로 청국장 분말을 첨가한 식이) 및 상황버섯 청국장군(고지방식이에 단백질원으로 상황버섯 청국장 분말을 첨가한 식이) 등 3군으로 나누어 5주간 사육한 결과는 다음과 같다. 실험동물의 체중은 대조군이 41.8 g 증가함에 비하여 청국장군 및 상황버섯 청국장군은 각 -3.7 g 및 -0.8 g으로 유의하게 감소되었고, 식이섭취량 및 식이효율은 대조군에 비하여 청국장군들이 유의하게 감소되었다. 간과 부고환지방의 무게 및 간조직의 콜레스테롤과 중성지질 농도는 대조군에 비하여 청국장군 및 상황버섯 청국장군이 유의하게 감소시키는 효과가 나타났다. 혈청의 중성지질, 총 콜레스테롤, LDL-콜레스테롤, VLDL-콜레스테롤 농도 및 동맥경화지수는 대조군에 비해 청국장군 및 상황버섯 청국장군이 유의하게 감소되었다. 총 콜레스테롤에 대한 HDL-콜레스테롤의 비율은 대조군에 비해 청국장군들이 유의하게 증가되었다. 변의 무게, 총 지질, 중성지질 및 콜레스테롤 배설량은 청국장군들이 대조군보다 유의하게 증가된 것으로 나타났다. 이상의 결과로 보아 고지방식이에 청국장 및 상황버섯 청국장 분말을 첨가 섭취시 혈청과 간조직의 중성지질, 총 콜레스테롤과 LDL-콜레스테롤 농도 및 동맥경화지수를 낮추고, 총 콜레스테롤에 대한 HDL-콜레스테롤의 비율을 증가시키는 지질대사의 개선 효과가 나타났다.

감귤부산물을 급여한 제주 개량흑돼지 고기가 흰쥐의 지질대사, 단백질 농도 및 효소활성에 미치는 영향

감귤피를 먹이지 않은 개량흑돼지 고기<TEX>$(T_0)$</TEX>와 성장기와 비육기에 감귤피를 각각 <TEX>$6\%$</TEX> 및 <TEX>$10\%$</TEX> 먹인 개량흑돼지 고기<TEX>$(T_1)$</TEX>를 첨가하여 식이를 제조하고 흰쥐에 급여했을 때에, 두식이 사이에 횐쥐의 증체량, 식이섭취량, 식이효율, 장기(간, 신장, 비장, 부고환 지방)무게, 혈청의 지질함량 중 총 지질, 인지질, 중성지질, 총콜레스테롤 및 HDL-콜레스테롤, 간의 총 지질과 중성지질 함량, 그리고 혈청의 단백질, 혈당, 혈색소 함량 및 효소(<TEX>$\gamma-GTP$</TEX>, ALT, AST, ALP)활성은 모두 유의적 차이를 보이지 않아서 감귤피 첨가 사료를 먹인 돼지고기의 영향이 없었다. 그러나 간의 콜레스테롤 함량과 혈청의 LDL-콜레스테롤 함량은 감귤피 급여구가 유의적으로 낮게 나타나서(p<0.05) 지질대사의 개선 효과를 기대할 수 있었다. Diets consist of two different pork samples: pork of a Jeju crossbred black pig not fed with tangerine peel during finishing period <TEX>$(T_0)$</TEX>, and pork fed with <TEX>$6\%\;and\;10\%$</TEX> tangerine peel during growing and finishing period <TEX>$(T_1)$</TEX>, respectively. The effects of the diet on physiological activities of rats were studied by feeding 17 weeks old rats with the two diets for 4 weeks. The feed intake, weight gain, feed efficiency ratio, and weight of liver, kidney, spleen and epididymal fat pad for the rats were similar among the diets. The total lipid level and triglyceride of liver were similar among <TEX>$T_0$</TEX> and <TEX>$T_1$</TEX>. All of the diet groups showed similar trends in terms of the serum total lipid, phospholipid, triglyceride, total cholesterol and HDL-cholesterol level, and atherogenic index, hemoglobin level, and <TEX>$\gamma-GTP$</TEX>, ALT, AST and ALP activities. However, it was found that the cholesterol level of liver and the LDL-cholesterol of serum in <TEX>$T_1$</TEX>, was significantly lower than those in <TEX>$T_0(p<0.05)$</TEX>.

The Adipose Renin-Angiotensin System Modulates Systemic Markers of Insulin Sensitivity and Activates the Intrarenal Renin-Angiotensin System

Background. The adipose tissue renin-angiotensin system (RAS) contributes to regulation of fat mass and may also impact systemic functions such as blood pressure and metabolism. Methods and results. A panel of mouse models including mice lacking angiotensinogen, Agt (Agt-KO), mice expressing Agt solely in adipose tissue (aP2-Agt/Agt-KO), and mice overexpressing Agt in adipose tissue (aP2-Agt) was studied. Total body weight, epididymal fat pad weight, and circulating levels of leptin, insulin, and resistin were significantly decreased in Agt-KO mice, while plasma adiponectin levels were increased. aP2-Agt mice exhibited increased adiposity and plasma leptin and insulin levels compared to wild type (WT) controls. Angiotensinogen and type I Ang II receptor protein levels were also elevated in kidney of aP2-Agt mice. Conclusion. These findings demonstrate that alterations in adipose RAS activity significantly impact both local and systemic physiology in a way that may contribute to the detrimental health effects of obesity.

PYY[3-36] Administration Decreases the Respiratory Quotient and Reduces Adiposity in Diet-Induced Obese Mice

In rodents, weight reduction after peptide YY[3-36] (PYY[3-36]) administration may be due largely to decreased food consumption. Effects on other processes affecting energy balance (energy expenditure, fuel partitioning, gut nutrient uptake) remain poorly understood. We examined whether s.c. infusion of 1 mg/(kg x d) PYY[3-36] (for up to 7 d) increased metabolic rate, fat combustion, and/or fecal energy loss in obese mice fed a high-fat diet. PYY[3-36] transiently reduced food intake (e.g., 25-43% lower at d 2 relative to pretreatment baseline) and decreased body weight (e.g., 9-10% reduction at d 2 vs. baseline) in 3 separate studies. Mass-specific metabolic rate in kJ/(kg x h) in PYY[3-36]-treated mice did not differ from controls. The dark cycle respiratory quotient (RQ) was transiently decreased. On d 2, it was 0.747 +/- 0.008 compared with 0.786 +/- 0.004 for controls (P < 0.001); light cycle RQ was reduced throughout the study in PYY[3-36]-treated mice (0.730 +/- 0.006) compared with controls (0.750 +/- 0.009; P < 0.001). Epididymal fat pad weight in PYY[3-36]-treated mice was approximately 50% lower than in controls (P < 0.01). Fat pad lipolysis ex vivo was not stimulated by PYY[3-36]. PYY[3-36] decreased basal gallbladder emptying in nonobese mice. Fecal energy loss was negligible ( approximately 2% of ingested energy) and did not differ between PYY[3-36]-treated mice and controls. Thus, negative energy balance after PYY[3-36] administration in diet-induced obese mice results from reduced food intake with a relative maintenance of mass-specific energy expenditure. Fat loss and reduced RQ highlight the potential for PYY[3-36] to drive increased mobilization of fat stores to help meet energy requirements in this model.

운지버섯 배양액이 콜레스테롤 식이를 섭취한 흰쥐의 지질 대사에 미치는 영향

고콜레스테롤 혈증을 유도한 횐쥐에 운지버섯 균사체 배양액이 지질대사에 미치는 영향을 조사하고자, 생후 8주령의 Sprague-Dawley계 숫쥐에 대조식이군(<TEX>$20\%$</TEX>지방과 <TEX>$0.5\%$ </TEX>콜레스테롤을 첨가한 식이), 대조식이와 운지버섯의 균사체 배양액을 음료수에 <TEX>$30\%$</TEX> 및 <TEX>$40\%$</TEX>로 혼합 급여한 군(<TEX>$30\%$</TEX> 및 <TEX>$40\%$</TEX> 운지버섯군)등 3군으로 나누어 6주간 사육한 결과는 다음과 같다 실험동물의 체중은 <TEX>$30\%$</TEX> 및 <TEX>$40\%$</TEX> 운지버섯군이 대조군에 비해 다소 감소되었으나, 식이섭취량 및 식이효율은 대조군과 운지버섯군이 비슷한 수준을 유지하였다. 간, 신장 및 부고환지방의 무게는 대조군과 운지버섯군이 비슷하였다. 간의 콜레스테롤 및 중성지질 농도는 대조군에 비해 <TEX>$40\%$</TEX>운지버섯군이 유의하게 감소된 것으로 나타났다. 혈청의 총 콜레스테롤, LDL-콜레스테롤 농도 및 동맥경화지수는 대조군에 비하여 <TEX>$30\%$</TEX>및 <TEX>$40\%$</TEX> 운지버섯군이 유의하게 감소되었다 HDL-콜레스테롤/총 콜레스테롤 비율은 대조군에 비해 유의하게 증가되었다. 변의 총 지질 및 중성지방의 배설량은 대조군에 비해 운지버섯군이 유의하게 증가시키는 것으로 나타났다. 이상의 결과로 보아 고콜레스테롤 식이를 급여한 횐쥐에 운지버섯 균사체 배양액을 <TEX>$ 30\%$</TEX> 및 <TEX>$40\%$</TEX> 급여시 체중을 다소 감소시키고, 간의 콜레스테롤과 중성지질, 혈청의 총 콜레스테롤, LDL-콜레스테롤 농도 및 동맥경화지수를 낮추는 효과가 나타났다.X>로 가슴 및 다리육의 적색도가 비슷한 경향을 나타내었고, 사육일령에 따라서는 일정한 경향을 나타내지 않았다. 가열 감량은 가슴육에서 <TEX>$26.37\~28.79\%$</TEX>이고 다리육은 <TEX>$30.32\~31.32\%$</TEX>로 다리육에서 가열감량이 <TEX>$2\~4\%$</TEX> 증가한 것으로 나타내었다. 그러나, 사육일령에 따라서는 일정한 경향을 나타내지 않았다. 전단력은 가슴육에서 45일령이 <TEX>$2.20\;kg/0.5inch^2$</TEX>, 70일령 <TEX>$2.84\;kg/0.5inch^2$</TEX>로 사육일령이 증가함에 고기의 연도도 함께 증가하는 것으로 나타내었다.pH가 낮아 드립의 발생량이 많은 것으로 나타났다.am은 24시간째에 온도와 관계없이 안정한 것으로 나타났다. Ceftriaxone sodium을 TPN과 Y-site 혼합 후 1-2시간 이내에 침천이 형성되었고 Unasyn의 경우에는 12시간째에 침천이 형성되었다. 혼합액의 pH나 색상은 연구기간 동안 일정하였다. 이러한 연구결과에 기초할 때, aminophylline은 고영양수액제와 혼합가능하고 ceftriaxone과 Unasyn은 고양양수액제와 혼합시 최소 1시간 동안은 안정한 것으로 평가되었다. 부작용 없이 조사할 수 있었고, 근치적 국소요법의 일환으로 방사선 선량증가가 전체 생존기간 및 무진행 생존기간을 향상시킬 수 있을 것으로 기대한다.: 유방암치료에서 virtual wedge는 통상 사용하는 physical wedge에 비하여 주변 연부조직선량, 반대편 유방선량, 동측 페선량 및 심장선량을 감소시켜 급, 만성 방사선 부작용의 위험을 감소시킬 수 있는 임상적으로 매우 유용한 방법이며 또한 방사선조사시간을 단축시킴으로써 선형가속기의 부하를 줄일 수 The effects of liquid culture of Coriolus (C) versicolor on weight gain, food intakes, food efficiency ratios, serum and hepatic lipid concentrations were investigated in male rats fed the high cholesterol diets. Eight weeks old Sprague-Dawley rats were given three different types of diet for six weeks, respectively: a control diet (<TEX>$ 20\% fat +0.5 \% $</TEX> cholesterol), two kinds of C versicolor diet (control diet + <TEX>$ 30\% or 40\%$</TEX>C. versicozor in water) according to the levels of C. versicolor supplementation. The body weight gains of the rats fed <TEX>$ 30\% or 40\% $</TEX> C. versicolor diets were lower than those in the rats fed the control diet. The food intake, food efficiency ratios, and liver, kidney, epididymal fat pad weights of the rats fed <TEX>$ 30\% or 40\%$</TEX> C. versicoEer diets were similar to those of the rats fed the control diet. The concentrations of hepatic cholesterol and triglyceride in the rats fed <TEX>$ 30\% or 40\% $</TEX> C. versicolor diets were significantly lower than those in the rats fed the control diet. The concentrations in serum total cholesterol, LDL-cholesterol, and atherogenic index ratios were significantly lower in the rats fed <TEX>$ 30\% or 40\%$</TEX> C. versicolor diets compared to those fed the control diet. The HDL-cholesterol/total-cholesterol ratios was significantly higher in the rats fed <TEX>$ 30\% or 40\% $</TEX> C. versicolor diets compared to those fed the control diet. The fecal excretion of total lipid and triglyceride in the rats fed <TEX>$ 40\% $</TEX> C. versicolor diet was significantly higher than that of the rats fed the control diet. There were no significant difference found in the serum trigly-ceride, phospholipid and HDL-cholesterol concentrations among the experimental groups. These results showed that the C. versicolor feeding decreased the hepatic cholesterol, triglyceride, and the serum total cholesterol, LDL-cholesterol and atherogenic index, and increased the serum HDL-cholesterol/ total-cholesterol ratio of the rats.

Deficiency of PPARα disturbs the response of lipogenic flux and of lipogenic and cholesterogenic gene expression to dietary cholesterol in mouse white adipose tissue

PPARα-deficiency in mice fed a high-carbohydrate, low-cholesterol diet was associated with a decreased weight of epididymal adipose tissue and an increased concentration of adipose tissue cholesterol. Consumption of a high (2% w/w) cholesterol diet resulted in a further increase in the concentration of cholesterol and a further decrease in epididymal fat pad weight in PPARα-null mice, but had no effect in the wild-type. These reductions in fat pad weight were associated with an increase in hepatic triacylglycerol content, indicating that both PPARα-deficiency and cholesterol altered the distribution of triacylglycerol in the body. Adipose tissue de novo lipogenesis was increased in PPARα-null mice and was further enhanced when they were fed a cholesterol-rich diet; no such effect was observed in the wild-type mice. The increased lipogenesis in the chow-fed PPARα-null mice was accompanied paradoxically by lower mRNA expression of SREBP-1c and its target genes, acetyl-CoA carboxylase and fatty acid synthase. Consumption of a high-cholesterol diet increased the mRNA expression of these genes in the PPARα-deficient mice but not in the wild-type. De novo cholesterol synthesis was not detectable in the adipose tissue of either genotype despite a relatively high expression of the mRNA's encoding SREBP-2 and 3-hydroxy-3-methylglutaryl Coenzyme A reductase. The mRNA expression of these genes and of the LDL-receptor in adipose tissue of the PPARα-deficient mice was lower than that of the wild-type and was not downregulated by cholesterol feeding. The results suggest that PPARα plays a role in adipose tissue cholesterol and triacylglycerol homeostasis and prevents cholesterol-mediated changes in de novo lipogenesis.

Endurance exercise training increases insulin responsiveness in isolated adipocytes through IRS/PI3-kinase/Akt pathway

Endurance exercise training promotes important metabolic adaptations, and the adipose tissue is particularly affected. The aim of this study was to investigate how endurance exercise training modulates some aspects of insulin action in isolated adipocytes and in intact adipose tissue. Male Wistar rats were submitted to daily treadmill running (1 h/day) for 7 wk. Sedentary age-matched rats were used as controls. Final body weight, body weight gain, and epididymal fat pad weight did not show any statistical differences between groups. Adipocytes from trained rats were smaller than those from sedentary rats (205 +/- 16.8 vs. 286 +/- 26.4 pl; P < 0.05). Trained rats showed decreased plasma glucose (4.9 +/- 0.13 vs. 5.3 +/- 0.07 mM; P < 0.05) and insulin levels (0.24 +/- 0.012 vs. 0.41 +/- 0.049 mM; P < 0.05) and increased insulin-stimulated glucose uptake (23.1 +/- 3.1 vs. 12.1 +/- 2.9 pmol/cm(2); P < 0.05) compared with sedentary rats. The number of insulin receptors and the insulin-induced tyrosine phosphorylation of insulin receptor-beta subunit did not change between groups. Insulin-induced tyrosine phosphorylation insulin receptor substrates (IRS)-1 and -2 increased significantly (1.57- and 2.38-fold, respectively) in trained rats. Insulin-induced IRS-1/phosphatidylinositol 3 (PI3)-kinase (but not IRS-2/PI3-kinase) association and serine Akt phosphorylation also increased (2.06- and 3.15-fold, respectively) after training. The protein content of insulin receptor-beta subunit, IRS-1 and -2, did not differ between groups. Taken together, these data support the hypothesis that the increased adipocyte responsiveness to insulin observed after endurance exercise training is modulated by IRS/PI3-kinase/Akt pathway.

Antiobesity Effect of Baek-Kimchi (Whitish Baechu Kimchl) in Rats Fed High Fat Diet

Baek-kimchi (whitish baechu kimchi) was evaluated for anti-obesity properties and effects on triglyceride (TG) and cholesterol in blood and adipose tissues in rats fed a high fat (20%) diet, and compared to the similar effects of baechu kimchi. Baek-kimchi does not use red pepper powder but contains higher levels of sliced radish and pear than baechu kimchi. SD rats were raised for four weeks on either a normal diet (ND, based on the AIN-93M diet), high fat diet (HFD, supplemented with 16% lard oil in the ND), or HFD containing 5% baek-kimchi or 5% baechu kimchi. Feed consumption was not different among the groups, but weight gains were significantly lower in the groups fed either the normal diet or HFD with baek-kimchi or baechu kimchi diets than the group fed HFD alone. The weights of liver and epididymal and perirenal fat pads in baek-kimchi and baechu kimchi diet groups were lower than those of the HFD groups, but the baek-kimchi diet group had lower epididymal and perirenal fat pad weights than the baechu kimchi diet group (p＜0.05). The baechu kimchi dietary group also had significantly lower triglyceride and cholesterol contents in liver and epididymal and perirenal fat, reversing the higher levels seen in HFD. Baek-kimchi and baechu kimchi diets were also effective in lowering serum triglyceride and cholesterol levels (p＜0.05). These results suggest that baek-kimchi and baechu kimchi consumption can reverse the effects of HFD on weight gain and blood and tissue lipids, and that baek-kimchi is more effective than baechu kimchi. The greater effect is probably due to the higher content of radish and pear used in baek-kimchi.

CART peptide: central mediator of leptin-induced adipose tissue apoptosis?

Because of connections between CART peptide containing neurons and the sympathetic nervous system (SNS) and the possible role of the SNS in leptin-induced adipose apoptosis, CART may act as a downstream effector of leptin-induced adipose apoptosis. Male Sprague–Dawley rats received continuous intracerebroventricular (i.c.v.) infusion for 4 days of either artificial cerebrospinal fluid (aCSF, 12 μl/day), leptin (15 μg/day), or CART55-102 at 2.4 μg/day (CART2.4) or 9.6 μg/day (CART9.6). Food intake (FI) was decreased 10.8% for CART2.4, 41.9% for CART9.6 and 33.4% for leptin ( p<0.05). CART9.6 and leptin reduced meal size and meal number. Body weight (BW) was reduced by CART9.6 (14.6%) and leptin (11.6%) ( p<0.05), but not by CART2.4. CART9.6 and CART2.4, but not leptin, caused hypothermia, and CART9.6 inhibited physical activity ( p<0.05). Epididymal, inguinal and retroperitoneal fat pad weights were reduced ( p<0.05) by both CART treatments and leptin; CART9.6 also reduced gastrocnemius muscle weight (18.1%, p<0.05). Leptin, but not CART, increased serum free fatty acid concentrations by 31.1% ( p<0.05) and increased adipose apoptosis by 48% ( p<0.05). These data show that although leptin and CART55-102 have some similar actions, CART55-102 is probably not a mediator for leptin-induced adipose apoptosis in the brain.

Obesity and changes of alkaline phosphatase activity in the small intestine of 40- and 80-day-old rats subjected to early postnatal overfeeding or monosodium glutamate.

To investigate the relationship between development of obesity and the small intestinal functions two experimental models of male Wistar rats were used in the present work: 1) early postnatally overfed rats, nursed from birth to weaning in small litters (SL, 4 pups/nest), and 2) neonatally monosodium glutamate treated rats (MSG 2 mg/g b.w. administered s.c. for 4 days after birth) submitted to the same early nutritional manipulation. After weaning, all animals had free access to a standard pellet diet and at 40 and 80 days of age their body weight, body fat content and food consumption as well as changes of the brush-border-bound duodenal and jejunal alkaline phosphatase (AP) activity were compared with parameters of the offsprings raised under normal feeding conditions (NL, 8 pups/nest). At 40 and 80 days of age the postnatally overfed pups from SL nests became heavier, displayed a significantly increased epididymal plus retroperitoneal fat pad weight (P<0.01) and significantly higher AP activity in both segments of the small intestine (P<0.01) in comparison with rats nursed in NL nests, although their mean daily food intake did not differ from that of non-obese rats during the postweaning periods examined. In contrast, the same treatment of MSG rats had only a small effect on late appearance of obesity, i.e. in early postnatally overfed and normally fed MSG rats a similar pattern of body weight, food intake, adiposity and AP activity was found after weaning. The effect of MSG-treatment was also accompanied by the appearance of normophagia, hypophagia and stunted growth on day 40 and day 80, respectively. Moreover, the size of fat depots and the increase of brush-border-bound AP activity in MSG rats belonging to the SL and NL groups was quantitatively similar to the values size of these parameters observed in SL obese rats subjected to early postnatal overnutrition. These results indicate that postnatal nutritional experience (overnutrition) may represent a predisposing factor in control rats from small litters for the development of obesity in later life. Permanently increased small intestinal AP activity observed after weaning in both models of obesity when hyperphagia is not present suggest that these functional changes and associated alterations in food digestion could be a component of regulatory mechanisms contributing to the maintenance of their elevated body fat weight.

Central effects of rat versus mouse leptin: ingestive behavior and adipose apoptosis

Leptin decreases food intake, body weight and fat mass while sparing lean mass. Although mouse leptin (ML) and rat leptin (RL) are 95.9% identical, our impression from previous studies was that they were not equally potent in rats. Thus, in the present study, 0 μg (vehicle) or 10 μg of ML or RL was injected into the lateral ventricle of rats (eight per treatment) once a day for four consecutive days. Body temperature, body weight, food intake and water intake were measured daily. Intrascapular and perirenal brown fat pads, white fat tissues (retroperitoneal, epididymal and inguinal fat pads) and the gastrocnemius muscle were collected and weighed 24 h after the last treatments. Body temperature was not affected by either ML or RL. Both ML and RL caused significant reductions in food intake ( P<0.05), and there was no difference between them. ML and RL also similarly inhibited water intake on days 2 and 3 ( P<0.05). By day 5 both ML- and RL-treated rats had lost weight (11.6 and 15.4 g, respectively), while vehicle-treated rats gained weight (6.8 g). Weights of retroperitoneal and epididymal fat pads, but not other tissues, were reduced similarly by both leptin treatments ( P<0.05). However, an increased apoptotic response was detected in the retroperitoneal fat tissue of RL- but not ML-treated rats ( P<0.05). These results suggest that RL is more effective than ML in inducing apoptosis in retroperitoneal fat tissue after i.c.v. injection in rats.

Anti-Obesity Effect of a New Dietary Supplement Consisting of Hydroxycitrate, Carnitine and Red Pepper (3D-Relax Diet) in High-Fat Fed Rats

Anti-obesity effect of a new dietary supplement (3D-relax) in high-fat fed rats. The aim of this study was to assess the effects of 3D-relax; a proprietary formulation containing hydroxycitrate (233 mg/g), carnitine (150 mg/g) and red pepper (150 mg/g); on body weight, body fat, and serum lipids levels in rats fed a high-fat diet. Male SD 7-wk-old rats (n=8) were fed a high fat diet [52% total dietary energy (E%) from fat, 15.4 E% protein, 32.6E% carbohydrate] with or without 3D-relax administration (1 g/kg body weight/day) for 3 weeks. Administration of 3D-relax significantly reduced the increase in body weight compared to the group fed high fat without 3D-relax. Food efficiency ratio (FER) tended to be decreased with administration of 3D-relax, but was not significant. The perirenal and epididymal fat pad weights of rats administered 3D-relax were significantly lower than those of the high fat group that did not ingest 3D-relax during the 3 weeks. The oral administration of 3D-relax significantly increased HDL-cholesterol level and lowered total cholesterol level compared to those of high fat alone group. These results suggest that 3D-relax reduced body weight and fat gains, and those effects are presumably linked to its inhibitory effects on lipogenesis.

Pharmacogenetic Evidence That Cd36Is a Key Determinant of the Metabolic Effects of Pioglitazone

Pioglitazone, like other thiazolidinediones, is an insulin-sensitizing agent that activates the peroxisome proliferator-activated receptor gamma and influences the expression of multiple genes involved in carbohydrate and lipid metabolism. However, it is unknown which of these many target genes play primary roles in determining the antidiabetic and hypolipidemic effects of thiazolidinediones. To specifically investigate the role of the Cd36 fatty acid transporter gene in the insulin-sensitizing actions of thiazolidinediones, we studied the metabolic effects of pioglitazone in spontaneously hypertensive rats (SHR) that harbor a deletion mutation in Cd36 in comparison to congenic and transgenic strains of SHR that express wild-type Cd36. In congenic and transgenic SHR with wild-type Cd36, administration of pioglitazone was associated with significantly lower circulating levels of fatty acids, triglycerides, and insulin as well as lower hepatic triglyceride levels and epididymal fat pad weights than in SHR harboring mutant Cd36. Additionally, insulin-stimulated glucose oxidation in isolated soleus muscle was significantly augmented in pioglitazone-fed rats with wild-type Cd36 versus those with mutant Cd36. The Cd36 genotype had no effect on pioglitazone-induced changes in blood pressure. These findings provide direct pharmacogenetic evidence that in the SHR model, Cd36 is a key determinant of the insulin-sensitizing actions of a thiazolidinedione ligand of peroxisome proliferator-activated receptor gamma.

PPAR alpha is necessary for the lipopenic action of hyperleptinemia on white adipose and liver tissue.

Adenovirus-induced hyperleptinemia causes rapid disappearance of body fat in normal rats, presumably by up-regulating fatty acid oxidation within white adipocytes. To determine the role of peroxisomal proliferation-activated receptor (PPAR)alpha expression, which was increased during the rapid loss of fat, we infused adenovirus-leptin into PPAR alpha(-/-) and PPAR alpha(+/+) mice. Despite similar degrees of hyperleptinemia and reduction in food intake, epididymal fat pad weight declined 55% in wild-type but only 6% in PPAR alpha(-/-) mice; liver triacylglycerol fell 39% in the wild-type group but was unchanged in PPAR(-/-) mice. Carnitine palmitoyl transferase-1 mRNA rose 52% in the wild-type mice but did not increase in PPAR alpha(-/-) mice. PPAR gamma coactivator-1 alpha rose 3-fold in the fat and 46% in the liver of wild-type mice but was unchanged in PPAR alpha(-/-) mice. Although AMP-activated protein kinase could not be implicated in the lipopenic actions of hyperleptinemia, acetyl CoA carboxylase protein was reduced in the liver of wild-type but not in PPAR alpha(-/-) mice. Thus, in PPAR alpha(-/-) mice, up-regulation of carnitine palmitoyl transferase-1 mRNA in fat, down-regulation of acetyl CoA carboxylase in liver, and up-regulation of PPAR gamma coactivator-1 alpha mRNA in both tissues are abolished, as is the reduction in their triacylglycerol content.

Effects of soy protein supplemented with methionine on blood lipids and adiposity of rats

OBJECTIVE: The effects of soy protein isolate (SPI) versus casein on blood lipids and adiposity were investigated in rats fed methionine-equivalent diets. METHODS: Twenty-eight male Sprague-Dawley rats (230 to 250 g) were assigned in equal numbers to groups consuming SPI- or casein-based diets (20%) supplemented with l-methionine. After 28 d, blood was collected for triacylglycerol, total cholesterol, and high-density lipoprotein cholesterol assessment and epididymal fat pads were weighed. RESULTS: Food intake (519 ± 90 versus 490 ± 115 g), weight gain (144 ± 35 versus 133 ± 28 g), food efficiency ratio (0.29 ± 0.09 versus 0.28 ± 0.06), epididymal fat pad weights (5.409 ± 2.076 versus 4.768 ± 1.867 g), and serum concentrations of triacylglycerol (96.3 ± 41.8 versus 93.4 ± 37.4 mg/dL) and high-density lipoprotein cholesterol (32.6 ± 7.4 versus 33.8 ± 4.4 mg/dL) were similar between the casein and SPI groups, respectively. However, total cholesterol (73.8 ± 17.8 versus 59.3 ± 11.9 mg/dL) concentration was higher for the casein-fed rats than for the SPI-fed rats, respectively ( P < 0.05). CONCLUSIONS: These results suggest that methionine supplementation may eliminate the decreased fat deposition previously ascribed to soy protein; however, methionine did not abolish the commonly observed hypocholesterolemic effects of soy.

Effect of group vs. single housing on phenotypic variance in C57BL/6J mice.

To determine if group housing affects the variance of body composition parameters in a highly inbred mouse strain. Thirty 3-week-old male C57BL/6J mice were obtained from the Jackson Laboratory. Fifteen mice were housed individually, and 15 mice were housed in groups of 5/cage. Animals were fed ad libitum and maintained in the same room under a 12:12-hour light/dark photoperiod at 22 degrees C for 9 weeks. Animals were killed, and fat mass, soft-lean tissue mass, bone mineral density (BMD), and bone mineral content (BMC) were determined by DXA. At necropsy, weights of the paired epididymal fat pads, paired retroperitoneal fat pads, right inguinal fat pad, liver, kidneys, paired testes, and seminal vesicles were obtained. Relative to mice housed singly, group-housed mice showed significantly greater variance in percentage of body fat, testes weight, and BMC. Group-housed mice tended to show greater variance in liver weights and BMD. Mice housed singly were smaller, had less soft-lean tissue mass and BMC, and lower BMD when compared with group-housed mice. These results suggest that with respect to body composition parameters, mice housed singly are more similar to one another than are group-housed mice, most likely because of a reduction in environmental (predominately behavioral/social) effects. Thus, mice housed singly may be more representative of genotypic effects on body composition than group-housed mice. Whether other inbred strains of mice show similar responses to housing condition is unknown.

Effects of litter size on sympathetic activity in young adult rats.

Rearing animals in small litters induces a permanent increase in body weight and body fat. To determine whether changes in sympathoadrenal activity contribute to this effect, litter size was adjusted the day after birth and maintained until weaning at 21 days. Sympathetic nervous system (SNS) activity was measured in adult animals using [(3)H]norepinephrine ([(3)H]NE) turnover in peripheral tissues. Although litter size was without effect on [(3)H]NE turnover in chow-fed animals, acceleration of [(3)H]NE turnover by dietary sucrose was completely abolished in heart and attenuated in interscapular brown adipose tissue and kidney of rats reared in small litters. Body and epididymal fat-pad weights were heavier in rats reared in small litters; however, weight gain in response to dietary enrichment with sucrose did not differ as a function of litter size. Thus litter size alters dietary activation of the SNS, and this effect presumably reflects changes in central nervous system regulation.