scholarly journals High fat diet induces alterations to intraepithelial lymphocyte and cytokine mRNA in the small intestine of C57BL/6 mice

RSC Advances ◽  
2017 ◽  
Vol 7 (9) ◽  
pp. 5322-5330 ◽  
Author(s):  
Franco Robles E. ◽  
Pérez Vázquez V. ◽  
Ramírez Emiliano J. ◽  
González Amaro R. ◽  
López Briones S.
Keyword(s):  
Small Intestine ◽  
High Fat Diet ◽  
Intraepithelial Lymphocyte ◽  
Mrna Levels ◽  
High Fat ◽  
Cytokine Mrna

The aim of this work was to investigate the possible effect of high fat diet (HFD) induced obesity on iIEL subsets and their cytokine mRNA levels in C57BL/6 mice.

scholarly journals Extract of Wax Gourd Peel Prevents High-Fat Diet-Induced Hyperlipidemia in C57BL/6 Mice via the Inhibition of the PPARγPathway

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ming Gu ◽  
Shengjie Fan ◽  
Gaigai Liu ◽  
Lu Guo ◽  
Xiaobo Ding ◽  
...  
Keyword(s):  
Blood Glucose ◽  
High Fat Diet ◽  
Target Genes ◽  
Metabolic Diseases ◽  
Body Weight Gain ◽  
Fasting Blood Glucose ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
High Fat ◽  
Wax Gourd

Wax gourd is a popular vegetable in East Asia. In traditional Chinese medicine, wax gourd peel is used to prevent and treat metabolic diseases such as hyperlipidemia, hyperglycemia, obesity, and cardiovascular disease. However, there is no experimental evidence to support these applications. Here, we examined the effect of the extract of wax gourd peel (EWGP) on metabolic disorders in diet-induced C57BL/6 obese mice. In the preventive experiment, EWGP blocked body weight gain and lowered serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), liver TG and TC contents, and fasting blood glucose in mice fed with a high-fat diet. In the therapeutic study, we induced obesity in the mice and treated with EWGP for two weeks. We found that EWGP treatment reduced serum and liver triglyceride (TG) contents and fasting blood glucose and improved glucose tolerance in the mice. Reporter assay and gene expression analysis showed that EWGP could inhibit peroxisome proliferator-activated receptorγ(PPARγ) transactivities and could decrease mRNA levels of PPARγand its target genes. We also found that HMG-CoA reductase (HMGCR) was downregulated in the mouse liver by EWGP. Our data suggest that EWGP lowers hyperlipidemia of C57BL/6 mice induced by high-fat diet via the inhibition of PPARγand HMGCR signaling.

scholarly journals Differential organ-specific inflammatory response to progranulin in high-fat diet-fed mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maki Murakoshi ◽  
Tomohito Gohda ◽  
Eri Adachi ◽  
Saki Ichikawa ◽  
Shinji Hagiwara ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Kidney Injury ◽  
Proximal Tubules ◽  
Tubular Damage ◽  
Standard Diet ◽  
Mrna Levels ◽  
High Fat ◽  
Organ Specific

AbstractProgranulin (PGRN) has been reported to bind tumor necrosis factor (TNF) receptor and to inhibit TNFα signaling. We evaluated the effect of augmentation of TNFα signaling by PGRN deficiency on the progression of kidney injury. Eight-week-old PGRN knockout (KO) and wild-type (WT) mice were fed a standard diet or high-fat diet (HFD) for 12 weeks. Albuminuria, markers of tubular damage, and renal mRNA levels of inflammatory cytokines were higher in HFD-fed KO (KO-HFD) mice than in HFD-fed WT (WT-HFD) mice. Body weight, vacuolization in proximal tubules, and systemic and adipose tissue inflammatory markers were lower in the KO-HFD mice than in the WT-HFD mice. The renal megalin expression was lower in the KO mice than in the WT mice regardless of the diet type. The megalin expression was also reduced in mouse proximal tubule epithelial cells stimulated with TNFα and in those with PGRN knockdown by small interfering RNA in vitro. PGRN deficiency was associated with both exacerbated renal inflammation and decreased systemic inflammation, including that in the adipose tissue of mice with HFD-induced obesity. Improved tubular vacuolization in the KO-HFD mice might partially be explained by the decreased expression of megalin in proximal tubules.

scholarly journals Time-of-Day-Dependent Effects of Bromocriptine to Ameliorate Vascular Pathology and Metabolic Syndrome in SHR Rats Held on High Fat Diet

2021 ◽  
Vol 22 (11) ◽  
pp. 6142
Author(s):  
Michael Ezrokhi ◽  
Yahong Zhang ◽  
Shuqin Luo ◽  
Anthony H. Cincotta
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
High Fat Diet ◽  
Nitrosative Stress ◽  
Time Of Day ◽  
Vascular Pathology ◽  
Mrna Levels ◽  
High Fat ◽  
Nadph Oxidase 4

The treatment of type 2 diabetes patients with bromocriptine-QR, a unique, quick release micronized formulation of bromocriptine, improves glycemic control and reduces adverse cardiovascular events. While the improvement of glycemic control is largely the result of improved postprandial hepatic glucose metabolism and insulin action, the mechanisms underlying the drug’s cardioprotective effects are less well defined. Bromocriptine is a sympatholytic dopamine agonist and reduces the elevated sympathetic tone, characteristic of metabolic syndrome and type 2 diabetes, which potentiates elevations of vascular oxidative/nitrosative stress, known to precipitate cardiovascular disease. Therefore, this study investigated the impact of bromocriptine treatment upon biomarkers of vascular oxidative/nitrosative stress (including the pro-oxidative/nitrosative stress enzymes of NADPH oxidase 4, inducible nitric oxide (iNOS), uncoupled endothelial nitric oxide synthase (eNOS), the pro-inflammatory/pro-oxidative marker GTP cyclohydrolase 1 (GTPCH 1), and the pro-vascular health enzyme, soluble guanylate cyclase (sGC) as well as the plasma level of thiobarbituric acid reactive substances (TBARS), a circulating marker of systemic oxidative stress), in hypertensive SHR rats held on a high fat diet to induce metabolic syndrome. Inasmuch as the central nervous system (CNS) dopaminergic activities both regulate and are regulated by CNS circadian pacemaker circuitry, this study also investigated the time-of-day-dependent effects of bromocriptine treatment (10 mg/kg/day at either 13 or 19 h after the onset of light (at the natural waking time or late during the activity period, respectively) among animals held on 14 h daily photoperiods for 16 days upon such vascular biomarkers of vascular redox state, several metabolic syndrome parameters, and mediobasal hypothalamic (MBH) mRNA expression levels of neuropeptides neuropeptide Y (NPY) and agouti-related protein (AgRP) which regulate the peripheral fuel metabolism and of mRNA expression of other MBH glial and neuronal cell genes that support such metabolism regulating neurons in this model system. Such bromocriptine treatment at ZT 13 improved (reduced) biomarkers of vascular oxidative/nitrosative stress including plasma TBARS level, aortic NADPH oxidase 4, iNOS and GTPCH 1 levels, and improved other markers of coupled eNOS function, including increased sGC protein level, relative to controls. However, bromocriptine treatment at ZT 19 produced no improvement in either coupled eNOS function or sGC protein level. Moreover, such ZT 13 bromocriptine treatment reduced several metabolic syndrome parameters including fasting insulin and leptin levels, as well as elevated systolic and diastolic blood pressure, insulin resistance, body fat store levels and liver fat content, however, such effects of ZT 19 bromocriptine treatment were largely absent versus control. Finally, ZT 13 bromocriptine treatment reduced MBH NPY and AgRP mRNA levels and mRNA levels of several MBH glial cell/neuronal genes that code for neuronal support/plasticity proteins (suggesting a shift in neuronal structure/function to a new metabolic control state) while ZT 19 treatment reduced only AgRP, not NPY, and was with very little effect on such MBH glial cell genes expression. These findings indicate that circadian-timed bromocriptine administration at the natural circadian peak of CNS dopaminergic activity (that is diminished in insulin resistant states), but not outside this daily time window when such CNS dopaminergic activity is naturally low, produces widespread improvements in biomarkers of vascular oxidative stress that are associated with the amelioration of metabolic syndrome and reductions in MBH neuropeptides and gene expressions known to facilitate metabolic syndrome. These results of such circadian-timed bromocriptine treatment upon vascular pathology provide potential mechanisms for the observed marked reductions in adverse cardiovascular events with circadian-timed bromocriptine-QR therapy (similarly timed to the onset of daily waking as in this study) of type 2 diabetes subjects and warrant further investigations into related mechanisms and the potential application of such intervention to prediabetes and metabolic syndrome patients as well.

scholarly journals Inactivation of the adrenergic receptor β2 disrupts glucose homeostasis in mice

2014 ◽  
Vol 221 (3) ◽  
pp. 381-390 ◽  
Author(s):  
Gustavo W Fernandes ◽  
Cintia B Ueta ◽  
Tatiane L Fonseca ◽  
Cecilia H A Gouveia ◽  
Carmen L Lancellotti ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Expenditure ◽  
Glucose Homeostasis ◽  
High Fat Diet ◽  
Liver Steatosis ◽  
Mrna Levels ◽  
High Fat ◽  
Adaptive Thermogenesis ◽  
Brown Adipose ◽  
Similar Body

Three types of beta adrenergic receptors (ARβ1–3) mediate the sympathetic activation of brown adipose tissue (BAT), the key thermogenic site for mice which is also present in adult humans. In this study, we evaluated adaptive thermogenesis and metabolic profile of a mouse withArβ2knockout (ARβ2KO). At room temperature, ARβ2KO mice have normal core temperature and, upon acute cold exposure (4 °C for 4 h), ARβ2KO mice accelerate energy expenditure normally and attempt to maintain body temperature. ARβ2KO mice also exhibited normal interscapular BAT thermal profiles during a 30-min infusion of norepinephrine or dobutamine, possibly due to marked elevation of interscapular BAT (iBAT) and ofArβ1, andArβ3mRNA levels. In addition, ARβ2KO mice exhibit similar body weight, adiposity, fasting plasma glucose, cholesterol, and triglycerides when compared with WT controls, but exhibit marked fasting hyperinsulinemia and elevation in hepaticPepck(Pck1) mRNA levels. The animals were fed a high-fat diet (40% fat) for 6 weeks, ARβ2KO mice doubled their caloric intake, accelerated energy expenditure, and inducedUcp1expression in a manner similar to WT controls, exhibiting a similar body weight gain and increase in the size of white adipocytes to the WT controls. However, ARβ2KO mice maintain fasting hyperglycemia as compared with WT controls despite very elevated insulin levels, but similar degrees of liver steatosis and hyperlipidemia. In conclusion, inactivation of the ARβ2KO pathway preserves cold- and diet-induced adaptive thermogenesis but disrupts glucose homeostasis possibly by accelerating hepatic glucose production and insulin secretion. Feeding on a high-fat diet worsens the metabolic imbalance, with significant fasting hyperglycemia but similar liver structure and lipid profile to the WT controls.

Abstract 15228: Hyperleptinemia Exacerbates High Fat Diet-mediated Atrial Remodeling and Fibrillation

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yuki Ebata ◽  
Akira Fukui ◽  
Hidekazu Kondo ◽  
Shotaro Saito ◽  
Ichitaro Abe ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Electrophysiological Study ◽  
Leptin Resistance ◽  
Atrial Remodeling ◽  
Conduction Time ◽  
Mrna Levels ◽  
High Fat ◽  
Perfused Heart ◽  
Calmodulin Kinase ◽  
Plasma Leptin

Introduction: Obesity is an independent risk factor of atrial fibrillation (AF). Although serum leptin levels have been reportedly up-regulated in subjects with obesity and metabolic syndrome (leptin resistance), the relation of hyperleptinemia and AF remains to be solved. Hypothesis: We tested the hypothesis whether hyperleptinemia could exacerbate high-fat-diet (HFD)-mediated AF. Methods: Eight-week-old male C57BL/6 (WT) and leptin-deficient ob/ob mice (Ob) were treated either with normal-fat-diet (NFD) or 60% HFD. Eight weeks later, transesophageal burst pacing and electrophysiological study using isolated perfused hearts were performed. The effect of leptin antagonist (LAnt) was also examined using osmotic mini-pump in WT-HFD mice. Results: 1) HFD increased body weight and plasma leptin concentration in WT mice (both p<0.01). 2) Masson trichrome staining revealed that heterogeneous interstitial LA fibrosis was evident in WT-HFD, which was not observed in Ob-HFD (p<0.05). Up-regulation of collagen1, α-SMA, TNF-α, and MCP-1 mRNA levels observed in WT-HFD mice LA, was attenuated in Ob-HFD mice. 3) While transesophageal burst pacing invariably induced AF (8/8, 100%) in WT-HFD mice, it induced AF less frequently (1/8, 12.5%) in Ob-HFD mice (p<0.01). 4) In isolated perfused heart experiments, interatrial conduction time was prolonged in WT-HFD mice, but not in Ob-HFD mice (p<0.05). 5) Western immunoblotting revealed up-regulated expressions of phosphorylated-calmodulin kinase II (p-CamKII) and Na+-Ca2+ exchanger in WT-HFD mice (both p<0.01). However, these changes were attenuated in Ob-HFD mice. 6) LAnt treatment for 4 weeks attenuated the AF inducibility assessed by transesophageal burst pacing (8/8 vs 2/8, p<0.05). Conclusions: Our findings suggest that hyperleptinemia (leptin resistance) plays an essential role in HFD-mediated atrial remodeling and AF. Inhibition of leptin or leptin signaling may become a novel therapeutic target to prevent obesity-related AF.

scholarly journals Defective dietary fat processing in transgenic mice lacking aquaporin-1 water channels

2001 ◽  
Vol 280 (1) ◽  
pp. C126-C134 ◽  
Author(s):  
Tonghui Ma ◽  
Sujatha Jayaraman ◽  
Kasper S. Wang ◽  
Yuanlin Song ◽  
Baoxue Yang ◽  
...  
Keyword(s):  
Small Intestine ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Water Channels ◽  
Wild Type ◽  
High Fat ◽  
Microvascular Endothelium ◽  
Aquaporin 1 ◽  
Pancreatic Fluid ◽  
Fat Processing

Immunocytochemistry showed expression of aquaporin-1 (AQP1) water channels at sites involved in dietary fat processing, including intrahepatic cholangiocytes, gallbladder, pancreatic microvascular endothelium, and intestinal lacteals. To determine whether AQP1 has a role in dietary fat digestion and/or absorption, mice were placed on a diet that contained 50% fat. Whereas wild-type mice (3–3.5 wk of age, 10–12 g) gained 49 ± 5% (SE, n = 50) body weight in 8 days, and heterozygous mice gained 46 ± 4%, AQP1 null mice gained only 4 ± 3%; weights became similar after return to a 6% fat diet after 6 days. The null mice on a high-fat diet acquired an oily appearance, developed steatorrhea with increased stool triglyceride content, and manifested serum hypotriglyceridemia. Supplementation of the high-fat diet with pancreatic enzymes partially corrected the decreased weight gain in null mice. Absorption of [14C]oleic acid from small intestine was not affected by AQP1 deletion, as determined by blood radioactivity after duodenal infusion. Lipase activity in feces and small intestine was remarkably greater in AQP1 null than wild-type mice on low- and high-fat diets. Fluid collections done in older mice (that are less sensitive to a high-fat diet) by ductal cannulation showed threefold increased pancreatic fluid flow in response to secretin/cholecystokinin, but volumes, pH, and amylase activities were affected little by AQP1 deletion, nor were bile flow rates and bile salt concentrations. Together, these results establish a dietary fat misprocessing defect in AQP1 null mice.

scholarly journals Dihydropyranocoumarins Exerted Anti-Obesity Activity In Vivo and its Activity Was Enhanced by Nanoparticulation with Polylactic-Co-Glycolic Acid

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 3053
Author(s):  
Hossin ◽  
Inafuku ◽  
Oku
Keyword(s):  
High Fat Diet ◽  
Glycolic Acid ◽  
Body Weight Gain ◽  
Oral Intake ◽  
Mrna Levels ◽  
High Fat ◽  
Mean Size ◽  
The Mean ◽  
Plga Nanoparticle

Dihydropyranocoumarins (DPCs) were isolated from Peucedanum japonicum Thunb as anti-obesity compounds in 3T3-L1 adipocytes assay; however, it is uncertain whether DPC exerts anti-obesity activity in vivo. Therefore, this study evaluated the oral intake of pure DPCs in mice fed a high-fat diet, and also attempted to enhance its activity by nanoparticulation. Increases in body weight gain and fat accumulation in white adipose tissues were significantly suppressed by the dietary intake of DPCs (1.943 mg/mouse/day). DPCs intake also significantly decreased the mean size of adipocytes and upregulated mRNA levels of thermogenesis-related genes. Nanoparticulation of DPCs with polylactic-co-glycolic acid (PLGA) dramatically increased its activity almost 100-fold over that of a non-nanoparticulated form. Thus, our findings clearly demonstrated the anti-obesity activity of DPCs in vivo and suggested that PLGA nanoparticle encapsulation was useful to enhance the anti-obesity activity of DPCs with the aim to develop natural and safe anti-obesity agents.

SO023HEPATOCYTE GROWTH FACTOR (HGF) PRECLUDE HIGH-FAT DIET-INDUCED OBESITY AND IMPROVED INSULIN RESISTANCE IN MICE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Jun Muratsu ◽  
Yoshiaki Taniyama ◽  
Fumihiro Sanada ◽  
Atsuyuki Morishima ◽  
Katsuhiko Sakaguchi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Adipose Tissue ◽  
Growth Factor ◽  
Inflammatory Mediators ◽  
High Fat Diet ◽  
Neutralizing Antibody ◽  
Mrna Levels ◽  
Wild Type ◽  
High Fat

Abstract Background and Aims Obesity and its associated chronic inflammation in adipose tissue initiate insulin resistance, which is related to several pathologies including hypertension and atherosclerosis. Previous reports demonstrated that circulating hepatocyte growth factor (HGF) level was associated with obesity and type 2 diabetes. However, its precise role in obesity and related-pathology is unclear. Method In this experiment, cardiac-specific over-expression of human HGF in mice (HGF-Tg mice) which showed 4-5 times higher serum HGF levels than wild-type mice were used. We chose cardiac specific HGF overexpression, as other strain of HGF transgenic mice such as liver and kidney specific HGF overexpression mice develop cancer and cystic diseases, which are rare in the heart. In the present study, using HGF-Tg mice and anti-HGF neutralizing antibody (HGF-Ab), we explored the role of HGF in obese and insulin resistance induced by high fat diet (HFD) for 14 weeks (200 or 400ug/week). Results With normal chow diet (ND), there were no significant changes in body weight between WT and HGF-Tg mice. While body weight in wild-type mice fed with HFD for 14 weeks was significantly increased accompanied with insulin resistance, HGF-Tg mice prevented body weight gain and insulin resistance. Insulin resistance in obesity arises from the combination of altered functions of insulin target cells (e.g., liver, skeletal muscle, and adipose tissue) and the accumulation of macrophages that secrete pro-inflammatory mediators in adipose tissue. The accumulation of macrophages and elevated levels of inflammatory mediators in adipose tissue were significantly inhibited in HGF-Tg mice as compared to wild-type mice. In the gWAT, the mRNA levels of the mature macrophage marker F4/80, the chemoattractants, MCP-1 and CXCL2, and the inflammatory cytokines, such as TNF-α and iNOS, were significantly increased in WT mice fed with HFD. However, these levels were markedly reduced in HGF-Tg mice fed with HFD. Additionally, activation of Akt by insulin administration was significantly reduced in the gWAT SM, and liver by HFD; however, this activation was restored in HGF-Tg mice. Moreover, insulin-induced Akt signaling was decreased in HGF-Ab groups as compared to saline group under HFD condition. Importantly, HFD significantly increased the level of HGF mRNA by approximately 2 fold in gWAT, SM, and liver without changing cMet expression. All together, these data indicate that the HGF as one of the systemic gWAT, SM, and liver-derived growth factor plays a role in compensatory mechanism against insulin-resistance through the at least anti-inflammatory effect in adipose tissue. The HFD-induced obesity in wild-type mice treated with HGF-neutralizing antibody showed an exacerbated response to the glucose tolerance test. Conclusion HGF suppresses inflammation in adipose tissue induced by a high-fat diet, and as a result improves systemic insulin resistance. These gain-of-function and loss-of-function studies demonstrated that the elevated HGF level induced by HFD have protective role against obesity and insulin resistance.

scholarly journals Hot Water Extract of Mulberry Leaf Ameliorates Hepatic Fat Accumulation and Inflammation in Rats Fed a High-Fat Diet

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 415-415
Author(s):  
Jibin Kim ◽  
Chaemin Kim ◽  
Mak-Soon Lee ◽  
Hyunmi Ko ◽  
Soojin Lee ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Water Extract ◽  
Density Lipoprotein ◽  
Hot Water ◽  
Mrna Levels ◽  
High Fat ◽  
Fat Accumulation ◽  
Mulberry Leaf ◽  
Hot Water Extract ◽  
Hepatic Fat

Abstract Objectives This study was conducted to investigate the effect of mulberry leaf extract on hepatic fat accumulation and inflammation in rats fed a high-fat diet. Methods Male Sprague–Dawley rats were randomly divided into three groups. Each group fed normal diet (NOR), high-fat diet (HF), or HF supplemented with 0.8% (w/w) hot water extract of mulberry leaf (HF + ME) for 14 weeks. Results The mulberry extract (ME) supplementation reduced body weight and white adipose tissues (epididymal, retroperitoneal, and mesenteric) weights. Serum levels of triglyceride (TG), total cholesterol (TC), free fatty acids (FFAs), and low-density lipoprotein cholesterol (LDL-C) were lower, while high-density lipoprotein cholesterol (HDL-C) level was higher in the HF + ME group compared to the HF group. The ME reduced the hepatic total lipid, TG, and TC levels compared to the HF group. The mRNA levels of genes related to fatty acid synthesis, such as CD36, sterol regulatory element binding protein 1c (SREBP-1c), and fatty acid synthase (FAS) were down-regulated by the ME supplementation. In addition, the ME lowered the mRNA levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), compared to the HF group. The serum TNF-α level of the HF + ME group was significantly lower than that of the HF group. Conclusions These results suggested that the ME attenuated high-fat diet-induced hepatic fat accumulation and inflammation via regulating gene expression related to hepatic lipid metabolism and pro-inflammatory mediators. Therefore, it is postulated that the ME might be useful as a functional food ingredient to prevent obesity-induced hepatic fat accumulation and inflammation. Funding Sources None.

scholarly journals Developmental and nutritional changes of ob and PPARγ2 gene expression in rat white adipose tissue

1997 ◽  
Vol 321 (2) ◽  
pp. 451-456 ◽  
Author(s):  
Véronique ROUSSEAU ◽  
Dominique J. BECKER ◽  
Lumbe N. ONGEMBA ◽  
Jacques RAHIER ◽  
Jean-Claude HENQUIN ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cell Size ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Diet Composition ◽  
Mrna Levels ◽  
Fat Pad ◽  
High Fat ◽  
High Carbohydrate ◽  
Fas Mrna

The ob gene encodes leptin, a hormone which induces satiety and increases energy expenditure. The peroxisome proliferator-activated receptor γ2 isoform (PPARγ2) gene encodes a transcription factor which controls adipocyte differentiation and expression of fat-specific genes. We have studied the regulation of these two genes in white adipose tissue (WAT) during the sucklingŐweaning transition. Suckling rats ingest a high-fat diet (milk). Fat-pad weight barely varied during the last week of suckling. ob mRNA levels, which were very low in 15-day-old rats, rose ∼ 6-fold until weaning at 21 days. When the rats were weaned on to a standard (high-carbohydrate) laboratory chow, epididymal WAT enlarged ∼ 7-fold, and ob mRNA kept increasing progressively and doubled between 21 and 30 days. This evolution contrasted with that of fatty acid synthase (FAS) mRNA, which increased sharply, but only after weaning. To distinguish between the influence of developmental and nutritional factors on ob expression, a group of rats was weaned on to a high-fat diet. This prevented the rise in glycaemia and insulinaemia and the decrease in plasma non-esterified fatty acids which otherwise occurred at weaning. This also resulted in a slight (10Ő15%) decrease in food intake and body weight gain. Under this high-fat diet, the rise of ob mRNA in WAT was augmented (3.7-fold in 30- versus 21-day-old pups), whereas the normal rise in FAS mRNA levels was attenuated. Fat-pad weights and adipocyte cell size and number were roughly similar in high-carbohydrate- and high-fat-weaned pups. mRNA levels of PPARγ2, like those of ob, were low in the WAT of 15-day-old suckling pups, doubled at 21 days, and reached a maximum as soon as 23 days. This evolution further differed from that of ob mRNA in not being influenced by diet composition. In conclusion, ob expression markedly increases during the sucklingŐweaning transition, and this effect is accentuated by a high-fat diet. Qualitative nutritional changes in ob mRNA were correlated with neither acute changes in adipose-tissue mass, nor cell size/number, nor variations in insulinaemia. PPARγ2 also increased during suckling, but rapidly reached a plateau after weaning and no longer changed thereafter. Unlike ob, PPARγ2 was not influenced by the diet composition.

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