Mesenteric Fat Pads Research Articles

Anti-obesity activity of chloroform-methanol extract of Premna integrifolia in mice fed with cafeteria diet.

Aim of the study:Aim of the present study was to evaluate the anti-obesity activity of chloroform:methanol extract of P. integrifolia (CMPI) in mice fed with cafeteria diet.Materials and Methods:Female Swiss Albino mice were divided into six groups, which received normal and cafeteria diet, standard drug simvastatin (10 mg/kg) and CMPI (50, 100 and 200 mg/kg) daily for 40 days. Parameters such as body weight, body mass index (BMI), Lee index of obesity (LIO), food consumption, locomotor behavior, serum glucose, triglyceride, total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), atherogenic index, organ weight and organ fat pad weight were studied for evaluating the anti-obesity activity of P. integrifolia. High performance liquid chromatography (HPLC) fingerprint profile of chloroform-methanol extract was also studied using quercetin as the reference standard.Results:There was a significant increase in body weight, BMI, LIO, food consumption, organ weight (liver and small intestine), organ fat pad weight (mesenteric and peri-renal fat pad) and in the levels of serum glucose, triglyceride, total cholesterol, LDL and VLDL with a significant decrease in locomotor behavior (ambulation, rearing, grooming) and HDL level in cafeteria diet group. Animals treated with CMPI showed dose dependent activity. P. integrifolia (200 mg/kg) supplementation attenuated all the above alterations, which indicates the anti-obesity activity. HPLC fingerprint profile of CMPI showed two peaks in the solvent system of 50 mm potassium diphosphate (pH-3 with ortho phosphoric acid): Methanol (30:70 v/v) at 360 nm.Conclusion:Present findings suggest that, CMPI possessed anti-obesity activity that substantiated its ethno-medicinal use in the treatment of obesity.

Superior mesenteric artery compression syndrome - case report

Superior mesenteric artery syndrome is an entity generally caused by the loss of the intervening mesenteric fat pad, resulting in compression of the third portion of the duodenum by the superior mesenteric artery. This article reports the case of a patient with irremovable metastatic adenocarcinoma in the sigmoid colon, that evolved with intense vomiting. Intestinal transit was carried out, which showed important gastric dilation extended until the third portion of the duodenum, compatible with superior mesenteric artery syndrome. Considering the patient's nutritional condition, the medical team opted for the conservative treatment. Four months after the surgery and conservative measures, the patient did not present vomiting after eating, maintaining previous weight. Superior mesenteric artery syndrome is uncommon and can have unspecific symptoms. Thus, high suspicion is required for the appropriate clinical adjustment. A barium examination is required to make the diagnosis. The treatment can initially require gastric decompression and hydration, besides reversal of weight loss through adequate nutrition. Surgery should be adopted only in case of clinical treatment failure.

Abstract 1824: Effects of high-fat diet feeding on solid tumor growth and lung metastasis in the Lewis lung cancer allograft model

Abstract Epidemiological studies indicate that overweight and obesity are associated with increased risk of developing several cancers. In the present study, we determined whether a chronic consumption of a high-fat diet increases solid tumor growth and metastasis in the C57BL/6N mouse lung cancer allograft model. Four-week old, male C57BL/6N mice were fed a purified diet containing 34.9% (w/w) fat (high fat diet) or 4.3 % fat (control diet) for 16 weeks, and then Lewis lung carcinoma cells were subcutaneously injected at 5 × 104 cells per mouse into the animals’ left flank. The primary tumor was resected 3 weeks later, and all animals were killed 21 days after the surgery. The high-fat diet feeding significantly increased the body weights and energy intakes as compared with those in the control diet group. The weights of the liver, spleen, epididymal fat pad, and mesenteric fat pad were increased in the high-fat diet group compared to the control group. The high fat diet increased solid tumor growth as well as the number and the size of colonies in the lung. Immunohistochemical staining of tumor tissues revealed that the expression of Ki67 (prototypic cell cycle related nuclear antigen), CD45 (phospho-tyrosine phosphatase), CD31 (platelet endothelial cell adhesion molecule-1), vascular endothelial growth factor (VEGF), cyclin-dependent kinase 4, cyclin A, and cyclin D1 was significantly increased in the high-fat diet group compared to the control group. The high-fat diet feeding significantly increased the blood levels of leptin, monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), granulocyte-colony stimulating factor (G-CSF), triggering receptor expressed on myeloid cells-1 (TREM-1), angiopoietin-1 (Ang-1), chemokine ligand 16 (CXCL16), plasminogen activator inhibitor-1 (PAI-1), and stromal cell-derived factor-1 (SDF-1) compared to the control group. Results of the present study indicate that the prolonged consumption of a high-fat diet enhances the secretion of cytokines, chemokines, matrix metalloproteinases, and angiogenesis-related proteins and increases the infiltration of macrophages into tumor tissues which, in turn, stimulate the proliferation and metastasis of lung cancer cells. The increased angiogenesis probably contributes to increased tumor growth and metastasis in mice fed on a high-fat diet. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1824. doi:10.1158/1538-7445.AM2011-1824

A suitable model to investigate the regeneration of transplanted hepatocytes

AimTo seek for a suitable site for isolated hepatocytes to proliferate with a high reliability, we established a mouse transplantation model and morphologically characterized the regeneration of transplanted ectopic hepatocytes.Materials & MethodsAdult male C57BL/6 mice were used as hepatocyte donors and hepatocytes were transplanted into mesenteric fat pads of C57BL/6‐Tg (CAG‐GFP) mice as recipients. At various times after transplantation of isolated hepatocytes (1.5×107 cells per site), mice were sacrificed and cryosections were made. Multiple‐immunostaining of various markers was employed for the 3‐dimentional imaging by the confocal laser‐scanning microscopy.Results & DiscussionThree weeks after transplantation, the transplanted hepatocytes vigorously regenerated to cell masses raging from 350μm to 2500μm in diameter. They are also acoompanied by the development of hepatic sinusoids of donor origin. The endotherial and type‐IV collagen linings of the sinusoids were comparable to those of the normal liver. Comparing with other transplantation sites, this model, therefore, provides a useful tool to investigate the regeneration of the liver structure and function after transplantation.

Metabolic and behavioral effects of chronic olanzapine treatment and cafeteria diet in rats

Olanzapine and highly palatable diets can alter metabolism and brain function. We investigated the interaction of chronic treatment (4 months) with olanzapine and a cafeteria diet on metabolic parameters, memory tasks (spatial and aversive), the elevated plus maze and locomotor activity induced by d-amphetamine. Male Wistar rats were separated into the following groups: standard diet vehicle, standard diet and olanzapine, cafeteria diet vehicle and cafeteria diet and olanzapine. Olanzapine was administered in the drinking water (approximately 1.5 mg/kg/day), and after 3 days of treatment, the rats exhibited an expected anxiolytic effect and reduced amphetamine-induced hyperlocomotion. After 4 months of treatment, cafeteria diet vehicle and cafeteria diet olanzapine rats exhibited an increased body weight and heavier fat pads compared with the standard diet groups. Olanzapine increased only the epididymal and mesenteric fat pads. The cafeteria diet and olanzapine group showed greater glucose intolerance compared with all other groups. The cafeteria diet altered the effects of chronic olanzapine on the performance in the water maze and inhibitory avoidance tasks. Chronic olanzapine treatment failed to affect amphetamine-induced locomotion and to produce anxiolytic effects in the elevated plus maze task, regardless of the diet. Our results suggest that chronic olanzapine caused an increase in fat pads, which is putatively involved in the etiology of many metabolic diseases. Rats on the cafeteria diet were overweight and exhibited glucose intolerance. We did not observe these effects with olanzapine treatment with the standard diet. Moreover, the chronic treatment regimen caused tolerance to the antipsychotic and anxiolytic effects of olanzapine and seemed to potentiate some of the metabolic effects of the cafeteria diet. The cafeteria diet also modified the effects of chronic treatment with olanzapine on cognitive tasks, which may represent an undesirable effect of poor diets in psychiatric patients.

A Case of Superior Mesenteric Artery Syndrome Secondary to Surreptitious Laxative Abuse

Purpose: Superior mesenteric artery (SMA) syndrome is an uncommon and controversial entity which refers to compression of the third portion of the duodenum between the SMA and the aorta. This is typically due to loss of the intervening mesenteric fat pad from significant weight loss. Here, we present a case of a young woman who developed SMA syndrome after extensive weight loss from surreptitious laxative abuse. A 29 year old female with no significant past medical history was referred to Woman's and Infant's Hospital for evaluation of a one year history of abdominal pain, diarrhea and new onset weight loss. The patient had previously had a comprehensive workup which included multiple lab tests, upper and lower endoscopy, RUQ ultrasound, upper GI series with small bowel follow through, CT scan of abdomen and pelvis, hepatobiliary scan and ultimately, a diagnostic laparoscopy. Outside of a mildly elevated lipase, the patient had a completely normal workup. Upon presentation to our hospital, the patient was ill appearing and extremely cachectic with a BMI of 14. Outside records were obtained, and the patient provided the same history as previously reported. Additionally, the patient denied any current or previous use of laxatives. The patient underwent MR enterography upon admission which demonstrated a new proximal small bowel obstruction with a dilated stomach. Additionally, a laxative abuse screen was sent upon admission as well. A CT scan of the abdomen and pelvis was obtained to further evaluate the proximal small bowel and stomach. This too demonstrated the dilated small bowel and stomach with an approximate measurement of the angle between the SMA and aorta to be less than 10 degrees. This was consistent with a diagnosis of SMA syndrome. The patient ultimately underwent laproscopic duodenaljejunal bypass to alleviate the obstruction. One day after discharge, the patient's laxative abuse screen reported to be positive for bisacodyl in both her urine and feces. She continued to deny any current or previous laxative use.Figure

Calpain-10 is a component of the obesity-related quantitative trait locus Adip1

Calpain-10 is a component of the obesity-related quantitative trait locus Adip1

Differences among white adipose tissue depots in mice

Excess white adipose tissue (WAT) is widely associated with insulin resistance, type 2 diabetes (T2D) and cardiovascular disease (CVD). In fact, intra‐abdominal fat is better correlated with insulin resistance than subcutaneous fat. However, the physiological impact of adipose depot location is not well understood. Our goal was to investigate cellular and molecular differences between WAT depots. Cell sizes and proteomic profiles from subcutaneous (inguinal) and intra‐abdominal (mesenteric, epididymal and retroperitoneal) fat pads from C57BL6/J mice were analyzed. Proteomes resolved by two‐dimensional gel electrophoresis followed by mass spectrometry showed significant differences in proteins involved in glycolysis, energy production, lipid transport, stress resistance, cytoskeleton structure, and others. Some of these proteins showed significant correlations to plasma insulin, leptin and/or adiponectin levels. Mean adipocyte cross‐sectional area was measured by digital image analysis of paraffin embedded tissue and was highest in epididymal and lowest in inguinal and mesenteric fat. Together, these results show marked differences among WAT depots, even within intra‐abdominal fat. This and further studies will help clarify the depot‐specific characteristics and their influence on insulin resistance in an effort to establish new diagnostic and/or therapeutic targets for T2D and CVD.Supported in part by the State of Ohio's Eminent Scholar Program that includes a gift from Milton and Lawrence Goll, by NIH Grants DK075436‐01, AG019899‐06, 1P01AG031736‐01A1, by the Diabetes Research Initiative and the BioMolecular Innovation and Technology Partnership at Ohio University, and by AMVETS.

Effect of Erythrina variegata seed extract on hyperlipidemia elicited by high-fat diet in wistar rats

Objective:To investigate the effect of the methanolic extract of Erythrina variegata (Linn.) var Orientalis (Fabaceae) seeds (MEEV) in reducing the cholesterol levels and as well as antioxidant in experimentally induced hyperlipidemic rats.Materials and Methods:Doses of 200 and 400 mg/kg of the extract were evaluated for its effect on lipid profile, HMG-CoA reductase, and on antioxidant enzymes in high-fat diet (HFD) induced hyperlipidemia.Results and Conclusion:The elevated levels of total cholesterol, triglycerides, low-density lipoprotein, and very low density lipoprotein due to HFD was reduced by concurrent treatment with MEEV (200 and 400 mg/kg) significantly (P<0.001). A significant reduction (P<0.001) in high-density lipoprotein was noticed in HFD fed groups; however, a nonsignificant increment was produced by the administration of MEEV (200 and 400 mg/kg). The HMG-CoA reductase activity was increased in HFD fed animals significantly (P<0.001) and was reduced by MEEV 400 mg/kg significantly (P<0.001). There was a noticed increase in the body weight and mesenteric fat pad weight in HFD fed group (P<0.001), which was reduced by the administration of MEEV (200 and 400 mg/kg). The antioxidant enzymes such as superoxide dismutase and catalase were reduced significantly in the HFD fed group, whose levels were increased significantly (P<0.001) by the administration of MEEV (200 and 400 mg/kg). Lipid peroxidation was increased in HFD fed animals, which was reduced significantly (P<0.001) by the treatment with MEEV (200 and 400 mg/kg).

Influence of dietary macronutrient composition on adiposity and cellularity of different fat depots in Wistar rats

The aim of this study was to investigate the role of dietary macronutrient content on adiposity parameters and adipocyte hypertrophy/hyperplasia in subcutaneous and visceral fat depots from Wistar rats using combined histological and computational approaches. For this purpose, male Wistar rats were distributed into 4 groups and were assigned to different nutritional interventions: Control group (chow diet); high-fat group, HF (60% E from fat); high-fat-sucrose group, HFS (45% E from fat and 17% from sucrose); and high-sucrose group, HS (42% E from sucrose). At day 35, rats were sacrificed, blood was collected, tissues were weighed and fragments of different fat depots were kept for histological analyses with the new softwareAdiposoft. Rats fed with HF, HFS and HS diets increased significantly body weight and total body fat against Control rats, being metabolic impairments more pronounced on HS rats than in the other groups. Cellularity analyses usingAdiposoft revealed that retroperitoneal adipose tissue is histologically different than mesenteric and subcutaneous ones, in relation to bigger adipocytes. The subcutaneous fat pad was the most sensitive to the diet, presenting adipocyte hypertrophy induced by HF diet and adipocyte hyperplasia induced by HS diet. The mesenteric fat pad had a similar but attenuated response in comparison to the subcutaneous adipose tissue, while retroperitoneal fat pad only presented adipocyte hyperplasia induced by the HS diet intake after 35 days of intervention. These findings provide new insights into the role of macronutrients in the development of hyperplastic obesity, which is characterized by the severity of the clinical features. Finally, a new tool for analyzing histological adipose samples is presented.

A resposta do peso e da composição corporal à inclusão da dieta de cafeteria e treinamento físico aeróbio em diferentes fases do desenvolvimento

The objective of this study was to identify the alterations in body weight and body composition related to the inclusion of cafeteria diet and aerobic physical training in different phases of the development. Wistar rats were used and divided in two experimental procedures, being one initiating with cafeteria diet and physical training with animals to the 21 days of life (sedentary cafeteria, SCa21; trained cafeteria, TCa21; sedentary control, SC21 and trained control TC21) and another one with cafeteria diet and physical training initiating to the 60 days of life (sedentary cafeteria, SCa; trained cafeteria, TCa; sedentary control, SC and trained control TC). After the experimental procedure, beyond the body weight, had been collected the periepididymal, retroperitoneal and mesenteric fat pads. The results had demonstrated a direct relation between physical inactivity, cafeteria diet and rise of the weight and fat pads of the studied regions. Also we got a positive reply to the inclusion of the physical training to the 21 days to it compares the group that after initiated physical training the 60 days, however the effect of the alimentary diet is primordial in the maintenance of one adjusted weight and corporal composition.

Regulation of Lipoprotein Lipase by Fasting in Epididymal and Mesenteric Adipocytes of Rats

There are marked variations in the activity of lipoprotein lipase (LPL) among adipose depots. The aim of this study was to compare the mechanisms of 24 h of fasting on LPL regulation between epididymal (EPI) adipocytes and mesenteric (MES) adipocytes in rats. 1-Day fasting consistently decreased activities of heparin-releasable LPL, total extractable LPL and cellular LPL markedly in both EPI and MES fat pads. LPL activity in MES fat pads was relatively lower than in the EPI fat pads. Consistent with data on LPL activity, the levels of expression of LPL mRNA in both nutritional states were lower in MES than EPI adipose tissue and isolated adipocytes. The decreased LPL activity after 1 day of fasting in MES adipocytes was explained mainly by a 50% decrease in the relative abundance of LPL mRNA level and a parallel 50% decrease in relative rate of LPL synthesis. In contrast, fasting of 1 day in EPI adipocytes decreased total LPL activity by 47% but did not affect LPL mRNA level or relative rate of LPL synthesis. A decrease in overall protein synthesis contributed to the decreased LPL activity after 1 day fasting both in EPI and MES adipocytes. In MES adipocytes the decrease in LPL activity, LPL mRNA and LPL synthesis were comparable, but in EPI adipocytes the changes in LPL activity were substantially larger than the changes in LPL mRNA level and LPL synthesis. Therefore, fasting decreased fat cell size, LPL activity, LPL mRNA level and relative rate of LPL synthesis in rats, and these effects were more marked in the MES adipocytes. These results clearly demonstrate the regional variations in the metabolic response of adipose tissue and LPL functions to fasting.

Exercise training decreases in vitro stimulated lipolysis in a visceral (mesenteric) but not in the retroperitoneal fat depot of high-fat-fed rats

The purpose of the present study was to determine the effects of an exercise training programme in high-fat-fed rats on in vitro lipolysis in a visceral (mesenteric) and a non-visceral fat depot (retroperitoneal) and its relationship to perilipin content. Two groups of female rats were fed a high-fat diet (42 % as energy) for 8 weeks, one remaining sedentary (Sed) and the other being exercise trained (Tr) for this entire period. Rats were killed after 2 and 8 weeks of their respective treatment. The significantly (P < 0.01) higher levels in mesenteric and retroperitoneal fat pad weights, plasma leptin, NEFA and glucose observed with time in Sed high-fat-fed rats were significantly (P < 0.05) attenuated in Tr animals. Isoproterenol-stimulated (10- 5-10- 4 m) lipolysis in the mesenteric, but not in the retroperitoneal tissue, was significantly (P < 0.05) lower (about 57 %) in Tr than in Sed rats after 8 weeks of high-fat feeding. The isoproterenol-stimulated lipolysis in the mesenteric tissue of 8-week Tr high-fat-fed rats was lowered to the level measured in 2-week fat-fed rats although mesenteric fat accumulation was still significantly (P < 0.01) higher in 8- than in 2-week Tr rats. Perilipin content (Western blot) was not affected by the exercise training programme. These results indicate that exercise training resulted in a reduction in the high-fat diet-induced elevated levels of lipolysis in the mesenteric tissue. This response appears to be independent of the perilipin content.

Assessment of the anti-obesity effects of the TNP-470 analog, CKD-732

The systemic treatment with angiogenesis inhibitor has been shown to result in weight reduction and adipose tissue loss in various models of obesity. To verify the mechanism of CKD-732 (TNP-470 analog) against obesity, we evaluated CKD-732's peripheral and central anti-obesity effects. CKD-732 was injected subcutaneously (s.c.) for 7 days in various animal models and intracerebroventricularly (i.c.v.) in arcuate nucleus (ARC) lesion mice, ob/ob mice, and normal littermates. Modulation of the hypothalamic neuropeptide mRNAs after i.c.v. injection was evaluated in ARC lesion mice and normal littermates. A conditioned taste aversion (CTA) was performed using lithium chloride (LiCl) as a positive control agent in Long-Evans Tokushima Otsuka and Otsuka Long-Evans Tokushima fatty (OLETF) rats. As a result, 7 days of CKD-732 s.c. injection reduced the cumulative food intake and the body weight significantly in both treated obese (e.g. 114.8 +/- 13.4 g vs 170.7 +/- 20.6 g, 7.9 +/- 0.5% decrease vs 0.3 +/- 2.2% decrease; in treated OLETF rat versus control OLETF rat, P < 0.01 respectively) and non-obese models. Epididymal and mesenteric fat pads, and the size of adipocytes were significantly decreased in treated rats. A single i.c.v. injection decreased food intake and body weight in ARC lesion mice and ob/ob mice but not in normal littermates. Unexpectedly, the hypothalamic neuropeptide mRNAs were not altered by single i.c.v. injection. CKD-732 also induced a dose-dependent CTA comparable with LiCl injection, which is a commonly used agent to produce a CTA. In conclusion, CKD-732 causes significant body weight and appetite reduction, possibly by decreasing adiposity directly and inducing central anorexia, which is partly explained by a CTA. These results should be carefully verified to assess the utility of CKD-732 as an anti-obesity drug.

Effects of fenofibrate on lipid metabolism in adipose tissue of rats

The effect of fenofibrate, a peroxisome proliferator–activated receptor α agonist, on body weight gain and on reduction of adipose tissue pads has been ascribed to increased fat catabolism in liver mainly through the induction of target enzymes involved in hepatic lipid metabolism. The aim of this study was to investigate whether peroxisome proliferator–activated receptor α activation also affects metabolic pathways in adipose tissue of rats treated with fenofibrate (100 mg/kg body weight) for 9 days. Fenofibrate lowered body weight gain and plasma triglyceride, total cholesterol, and high-density lipoprotein cholesterol but had no influence on food intake and on plasma glucose levels. The activity of lipoprotein lipase of treated animals decreased 50% in epididymal, 29% in retroperitoneal, and was not affected in the mesenteric fat pads. In this study, we show a 34% decrease in epididymal adipose tissue de novo lipogenesis by fenofibrate. The results demonstrate that insulin sensitivity of lipolysis is decreased in fenofibrate-treated rats which resulted in 30% higher rate of glycerol release when compared to the control group. These findings suggest that besides its effects on liver, fenofibrate exerts effects on lipid metabolism in adipose tissue which may contribute to decreasing adiposity.

Olanzapine-Induced Weight Gain and Increased Visceral Adiposity is Blocked by Melatonin Replacement Therapy in Rats

The atypical antipsychotic drug olanzapine increases body weight and visceral adiposity in schizophrenia. In rats, aging-associated increased body weight and visceral adiposity are reversed by administration of the pineal hormone melatonin. We asked if melatonin similarly would reverse olanzapine-induced increased weight and visceral adiposity in rats. Four groups (n=11/group) of female rats (240-250 g) were treated for 8 weeks with olanzapine, melatonin, olanzapine+melatonin, or vehicle alone in drinking water. Body weight and food and water consumption were determined weekly, locomotor activity at weeks 3 and 6, and nocturnal plasma melatonin concentration at week 7. At week 8, the rats were killed and visceral (perirenal, retroperitoneal, omental, and mesenteric) fat pads dissected and weighed. Olanzapine treatment reduced nocturnal plasma melatonin by 55% (p<0.001), which was restored to control levels by olanzapine+melatonin. Body weight increased 18% in rats treated with olanzapine alone, but only 10% with olanzapine+melatonin, 5% with melatonin alone, and 7% with vehicle control. Body weight and visceral fat pad weight increases in rats treated with olanzapine alone were greater than in each of the other three groups (all p<0.01), which were not significantly different. These results suggest that olanzapine-induced increases in body weight and visceral adiposity may be at least in part secondary to olanzapine-induced reduction of plasma melatonin levels, and that melatonin may be useful for the management of olanzapine-induced weight gain in humans.

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.

Sympathetic denervation does not prevent a reduction in fat pad size of rats or mice treated with peripherally administered leptin

Leptin increases sympathetic nervous system (SNS) activity in brown adipose tissue and renal nerves. Experiments described here tested whether SNS innervation is required for peripheral, physiological concentrations of leptin to reduce body fat. In experiment 1, one epididymal (EPI) fat pad was sympathectomized by local injection of 6-hydroxydopamine (6OHDA) in C57BL/6 mice that were then infused for 13 days with PBS or 10 microg leptin/day from an intraperitoneal miniosmotic pump. Surprisingly, EPI denervation increased total body fat of PBS-infused mice but leptin decreased the size of both injected and noninjected EPI pads in 6OHDA mice. Experiment 2 was identical except for the use of male Sprague-Dawley rats that were infused with 50 microg leptin/day. Leptin had little effect on EPI weight or norepinephrine (NE) content, but denervation of one EPI pad decreased the effect of leptin on intact EPI, inguinal and retroperitoneal (RP) fat and increased the size of the mesenteric fat pad. Experiment 3 included groups in which either one EPI or one RP pad was denervated. RP denervation reduced RP NE content but did not prevent a leptin-induced reduction in fat pad mass. Therefore, the SNS is not required for low doses of leptin to reduce body fat. EPI denervation significantly increased adipocyte number in contralateral EPI and RP fat pads and this was prevented by leptin. These changes in intact pads of rats with one denervated fat pad imply communication between fat depots and suggest that both leptin and the SNS regulate the size of individual depots.

Glucocorticoid-dependent stimulation of adiposity and appetite by a ghrelin mimetic in the rat

Chronic administration of GH secretagogues (GHSs) induces a state of positive energy balance in rodents by a GH-independent mechanism. Here we sought to determine to what extent the GHS effects to increase food intake and increase fat accumulation are glucocorticoid-dependent. The effects of twice-daily s.c. injections of GH-releasing peptide-6 (GHRP-6) (250 microg/kg) for 2 weeks on body weight, food intake and fat pad weight were determined in both adrenalectomised (ADX) rats (with or without basal corticosterone replacement) and adrenal-intact rats. All GHS-injected rats had a significantly increased body weight at the end of 2 weeks of treatment compared with saline controls. However, increased fat accumulation was only seen in adrenal-intact rats, with a 15% increase in s.c. inguinal (P<0.05 vs saline controls) and 20% increase in visceral mesenteric (P<0.05) fat pad weights following GHS treatment. The increased body weight observed in ADX rats following GHS treatment was not due to increased fat mass or increased weight of other organs measured. Food intake was increased for up to 7 h following a single injection of GHRP-6 in both the adrenal-intact (P<0.01) and corticosterone-replacement groups (P<0.05). This stimulating effect on food intake was not observed at any time point in the ADX rats without corticosterone replacement. These data suggest that GHS-induced body weight gain is glucocorticoid-independent. However, basal levels of glucocorticoids are permissive for the GHS-induced increase in food intake whilst activation of the hypothalamo-pituitary-adrenal axis appears to contribute to the GHS-induced accumulation of fat mass.

Compensatory Growth of Adipose Tissue After Partial Lipectomy: Involvement of Serum Factors

The regulation of body weight/fat was studied by investigating mechanisms for compensatory adipose tissue growth after removal of bilateral epididymal fat pads from male adult Wistar rats. Food intake during the first 4 weeks and energy expenditure on Days 8-10 postsurgery were not different between lipectomized and sham operated rats. During Days 29-31 post surgery, a small (2.4%) but significant (P < 0.05) increase in heat production per metabolic body size was detected in lipectomized as compared with sham operated rats. The carcass composition of lipectomized and sham operated rats was not significantly different 16 weeks after surgery. The compensatory growth was fat pad-specific: mesenteric, retroperitoneal, and inguinal fat pads, but not perirenal fat pads, were heavier in lipectomized rats than in sham operated rats as early as 4 weeks postsurgery. Examination of fat cell size distribution in the compensating pads indicated a shift toward larger cells in retroperitoneal fat, but not in inguinal fat of lipectomized as compared with sham operated rats. Serum from lipectomized rats, but not media conditioned by exposure to retroperitoneal fat pads from lipectomized rats, stimulated proliferation of preadipocytes in vitro more than that from sham operated rats. Thus, compensatory adipose tissue growth after lipectomy may be mediated, in part, by blood-borne factors that are derived from tissues other than adipose tissue.