Increased adiponectin receptor-1 expression in adipose tissue of impaired glucose-tolerant obese subjects during weight loss

Objective: To investigate the mRNA expression of adiponectin, AdipoR1 and AdipoR2, the two recently cloned adiponectin receptors and peroxisome proliferator activated receptor (PPAR)γ2 in adipose tissue of obese individuals before and during a very low calorie diet (VLCD) inducing weight loss. Methods: Twenty-three non-diabetic obese subjects with normal (NGT, n=11) or impaired glucose tolerance (IGT, n=12) (age, 47±3 years; body mass index, 39.3±1.3 kg/m2) were studied before and after a 3-week 3.9 MJ diet daily without exercise. mRNA levels of nine IGT and six NGT subjects were measured by real-time PCR in s.c. abdominal adipose tissue. Results: Metabolic parameters and insulin sensitivity were improved by VLCD in the IGT group, but minimally affected in the NGT group. VLCD increased expression of AdipoR1 in the IGT (P=0.02), but not in the NGT group. Adiponectin, AdipoR2 and PPARγ2 mRNA levels did not change during VLCD in any group. In the IGT, but not in the NGT group, AdipoR1 and AdipoR2 expressions were positively related to that of PPARγ2 and, after VLCD, AdipoR1 and AdipoR2 expressions were positively related to each other and to that of adiponectin. Conclusion: In the NGT group, the 3-week VLCD inducing weight loss did not modify metabolic parameters, insulin sensitivity and the expression of the adiponectin system in adipose tissue. By contrast, in the IGT group, AdipoR1 expression increased and we found a coordinate regulation of the expression of adiponectin and its receptors. These modifications could participate, through adiponectin action on adipocytes, to the improved metabolic parameters observed in IGT subjects.

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Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00110.2003 ◽

2003 ◽

Vol 285 (3) ◽

pp. E527-E533 ◽

Cited By ~ 438

Author(s):

Jens M. Bruun ◽

Aina S. Lihn ◽

Camilla Verdich ◽

Steen B. Pedersen ◽

Søren Toubro ◽

...

Keyword(s):

Weight Loss ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Mrna Levels ◽

Plasma Adiponectin ◽

Tnf Α ◽

Adiponectin Mrna ◽

Before And After

Adiponectin is an adipose tissue-specific protein that is abundantly present in the circulation and suggested to be involved in insulin sensitivity and development of atherosclerosis. Because cytokines are suggested to regulate adiponectin, the aim of the present study was to investigate the interaction between adiponectin and three adipose tissue-derived cytokines (IL-6, IL-8, and TNF-α). The study was divided into three substudies as follows: 1) plasma adiponectin and mRNA levels in adipose tissue biopsies from obese subjects [mean body mass index (BMI): 39.7 kg/m2, n = 6] before and after weight loss; 2) plasma adiponectin in obese men (mean BMI: 38.7 kg/m2, n = 19) compared with lean men (mean BMI: 23.4 kg/m2, n = 10) before and after weight loss; and 3) in vitro direct effects of IL-6, IL-8, and TNF-α on adiponectin mRNA levels in adipose tissue cultures. The results were that 1) weight loss resulted in a 51% ( P < 0.05) increase in plasma adiponectin and a 45% ( P < 0.05) increase in adipose tissue mRNA levels; 2) plasma adiponectin was 53% ( P < 0.01) higher in lean compared with obese men, and plasma adiponectin was inversely correlated with adiposity, insulin sensitivity, and IL-6; and 3) TNF-α ( P < 0.01) and IL-6 plus its soluble receptor ( P < 0.05) decreased adiponectin mRNA levels in vitro. The inverse relationship between plasma adiponectin and cytokines in vivo and the cytokine-induced reduction in adiponectin mRNA in vitro suggests that endogenous cytokines may inhibit adiponectin. This could be of importance for the association between cytokines (e.g., IL-6) and insulin resistance and atherosclerosis.

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PPAR-γ Gene Expression in Human Adipose Tissue Is Associated with Weight Loss After Sleeve Gastrectomy

Journal of Gastrointestinal Surgery ◽

10.1007/s11605-021-05216-6 ◽

2021 ◽

Author(s):

Jorge-Luis Torres ◽

Ricardo Usategui-Martín ◽

Lourdes Hernández-Cosido ◽

Edgar Bernardo ◽

Laura Manzanedo-Bueno ◽

...

Keyword(s):

Weight Loss ◽

Adipose Tissue ◽

Sleeve Gastrectomy ◽

Morbidly Obese ◽

Peroxisome Proliferator ◽

Obese Patients ◽

Peroxisome Proliferator Activated Receptor ◽

Clinical Variables ◽

Ppar Γ ◽

Obese Subjects

Abstract Background The peroxisome proliferator-activated receptor (PPAR)-γ plays a key role in adipose tissue differentiation and fat metabolism. However, it is unclear which factors may regulate its expression and whether obese patients have changes in adipose tissue expression of PPAR-γor potential regulators such as miR-27. Thus, our aims were to analyze PPAR-γ and miR-27 expression in adipose tissue of obese patients, and to correlate their levels with clinical variables. Subjects and Methods. We included 43 morbidly obese subjects who underwent sleeve gastrectomy (31 of them completed 1-year follow-up) and 19 non-obese subjects. mRNA expression of PPAR-γ1 and PPAR-γ2, miR-27a, and miR-27b was measured by qPCR in visceral and subcutaneous adipose tissue. Clinical variables and serum adipokine and hormone levels were correlated with PPAR-γ and miR-27 expression. In addition, a systematic review of the literature regarding PPAR-γ expression in adipose tissue of obese patients was performed. Results We found no differences in the expression of PPAR-γ and miR-27 in adipose tissue of obese patients vs. controls. The literature review revealed discrepant results regarding PPAR-γ expression in adipose tissue of obese patients. Of note, we described a significant negative correlation between pre-operative PPAR-γ1 expression in adipose tissue of obese patients and post-operative weight loss, potentially linked with insulin resistance markers. Conclusion PPAR-γ1 expression in adipose tissue is associated with weight loss after sleeve gastrectomy and may be used as a biomarker for response to surgery.

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Secretion of adiponectin multimeric complexes from adipose tissue explants is not modified by very low calorie diet

Acta Endocrinologica ◽

10.1530/eje-08-0727 ◽

2009 ◽

Vol 160 (4) ◽

pp. 585-592 ◽

Cited By ~ 12

Author(s):

Zuzana Kovacova ◽

Michaela Vitkova ◽

Michaela Kovacikova ◽

Eva Klimcakova ◽

Magda Bajzova ◽

...

Keyword(s):

Weight Loss ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Dietary Intervention ◽

Culture Media ◽

Very Low Calorie Diet ◽

Low Calorie Diet ◽

Total Adiponectin ◽

Calorie Diet ◽

Obese Subjects

ObjectiveAdiponectin is a protein abundantly secreted by the adipose tissue (AT). Plasma adiponectin levels are decreased in obese, insulin-resistant, and type 2 diabetic patients. Various multimeric complexes, i.e. high-, middle-, and low-molecular weight isoforms (HMW, MMW and LMW), are present in plasma. Here, we investigated the effect of weight reducing diet on the distribution of adiponectin isoforms in plasma and on their secretion in AT explants from obese subjects.DesignA total of 20 obese subjects (age 37.8±7.3 years, body mass index 33.9±5.0 kg/m2) underwent eight weeks of very low-calorie diet (VLCD). A needle biopsy of subcutaneous abdominal AT and blood samples were taken before and after dietary intervention. AT explants were incubated in culture medium for 4 h. ELISA assay and western blot analyses were used to identify adiponectin complexes in culture media and in plasma.ResultsThe distribution of adiponectin polymers in plasma was different from that secreted in human AT explants. Before VLCD, the relative amount of HMW isoform was 75.5±9.1% of total adiponectin in culture media and 52.2±11.2% in plasma. Despite the diet-induced weight loss and improvement of insulin sensitivity, VLCD neither induced change in total adiponectin level nor in the ratio of HMW to total adiponectin in plasma and in culture media of AT explants.ConclusionsThe profile of adiponectin polymeric isoforms secreted by AT explants into culture media differs from the plasma profile. A dietary intervention leading to weight loss and improvement of insulin sensitivity was not associated with modifications of AT secretion of total or HMW adiponectin.

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Regulation of human aldoketoreductase 1C3 (AKR1C3) gene expression in the adipose tissue

Cellular & Molecular Biology Letters ◽

10.2478/s11658-008-0025-6 ◽

2008 ◽

Vol 13 (4) ◽

Cited By ~ 19

Author(s):

Per-arne Svensson ◽

Britt Gabrielsson ◽

Margareta Jernås ◽

Anders Gummesson ◽

Kajsa Sjöholm

Keyword(s):

Gene Expression ◽

Metabolic Syndrome ◽

Weight Loss ◽

Adipose Tissue ◽

Mrna Levels ◽

Very Low Calorie Diet ◽

Metabolic Complications ◽

Realtime Pcr ◽

The Metabolic Syndrome ◽

Obese Subjects

AbstractAldoketoreductase 1C3 (AKR1C3) is a functional prostaglandin F synthase and a negative modulator of the availability of ligands for the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ). AKR1C3 expression is known to be associated with adiposity, one of the components of the metabolic syndrome. The aim of this study was to characterize the expression of AKR1C3 in the adipose tissue and adipocytes and to investigate its potential role in the metabolic syndrome. Using microarray analysis and realtime PCR, we studied the expression of AKR1C3 in adipose tissue samples from obese subjects with or without metabolic complications, during very low calorie diet-induced weight loss, and its expression in isolated human adipocytes of different sizes. The adipose tissue AKR1C3 expression levels were marginally lower in obese subjects with the metabolic syndrome compared with the levels in healthy obese subjects when analyzed using microarray (p = 0.078) and realtime PCR (p < 0.05), suggesting a secondary or compensatory effect. The adipose tissue mRNA levels of AKR1C3 were reduced during and after dietinduced weight-loss compared to the levels before the start of the diet (p < 0.001 at all time-points). The gene expression of AKR1C3 correlated with both adipose tissue mRNA levels and serum levels of leptin before the start of the diet (p < 0.05 and p < 0.01, respectively). Furthermore, large adipocytes displayed a higher expression of AKR1C3 than small adipocytes (1.5-fold, p < 0.01). In conclusion, adipose tissue AKR1C3 expression may be affected by metabolic disease, and its levels are significantly reduced in response to dietinduced weight loss and correlate with leptin levels.

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The role of the novel adipocyte-derived hormone adiponectin in human disease

Acta Endocrinologica ◽

10.1530/eje.0.1480293 ◽

2003 ◽

pp. 293-300 ◽

Cited By ~ 691

Author(s):

JJ Diez ◽

P Iglesias

Keyword(s):

Adipose Tissue ◽

Insulin Sensitivity ◽

Experimental Models ◽

Glucose Disposal ◽

Diabetic Patients ◽

Peroxisome Proliferator ◽

Complement Factor ◽

Mrna Levels ◽

Peroxisome Proliferator Activated Receptor ◽

Plasma Adiponectin

Adiponectin, also called GBP-28, apM1, AdipoQ and Acrp30, is a novel adipose tIssue-specific protein that has structural homology to collagen VIII and X and complement factor C1q, and that circulates in human plasma at high levels. It is one of the physiologically active polypeptides secreted by adipose tIssue, whose multiple functions have started to be understood in the last few Years.A reduction in adiponectin expression is associated with insulin resistance in some animal models. Administration of adiponectin has been accompanied by a reduction in plasma glucose and an increase in insulin sensitivity. In addition, thiazolidinediones, drugs that enhance insulin sensitivity through stimulation of the peroxisome proliferator-activated receptor-gamma, increase plasma adiponectin and mRNA levels in mice. On the other hand, this adipocyte protein seems to play a protective role in experimental models of vascular injury. In humans, adiponectin levels are inversely related to the degree of adiposity and positively associated with insulin sensitivity both in healthy subjects and in diabetic patients. Plasma adiponectin levels have been reported to be decreased in some insulin-resistant states, such as obesity and type 2 diabetes mellitus, and also in patients with coronary artery disease. On the contrary, chronic renal failure, type 1 diabetes and anorexia nervosa are associated with increased plasma adiponectin levels. Concentrations of plasma adiponectin have been shown to correlate negatively with glucose, insulin, triglyceride levels and body mass index, and positively with high-density lipoprotein-cholesterol levels and insulin-stimulated glucose disposal. Weight loss and therapy with thiazolidinediones increased endogenous adiponectin production in humans.Adiponectin increases insulin sensitivity by increasing tIssue fat oxidation, resulting in reduced circulating fatty acid levels and reduced intracellular triglyceride contents in liver and muscle. This protein also suppresses the expression of adhesion molecules in vascular endothelial cells and cytokine production from macrophages, thus inhibiting the inflammatory processes that occur during the early phases of atherosclerosis. In view of these data, it is possible that hypoadiponectinemia may play a role in the development of atherosclerotic vascular disease.In summary, the ability of adiponectin to increase insulin sensitivity in conjunction with its anti-inflammatory and anti-atherogenic properties have made this novel adipocytokine a promising therapeutic tool for the future, with potential applications in states associated with low plasma adiponectin levels.

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Adipose tissue production of hepatocyte growth factor contributes to elevated serum HGF in obesity

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00174.2006 ◽

2006 ◽

Vol 291 (4) ◽

pp. E843-E848 ◽

Cited By ~ 66

Author(s):

Lauren N. Bell ◽

Jennifer L. Ward ◽

Mikako Degawa-Yamauchi ◽

Jason E. Bovenkerk ◽

RoseMarie Jones ◽

...

Keyword(s):

Weight Loss ◽

Adipose Tissue ◽

Elevated Serum ◽

Mrna Levels ◽

Tissue Mass ◽

Tnf Α ◽

Before And After ◽

Obese Subjects ◽

Hepatocyte Growth

Serum HGF is elevated in obese individuals. This study examined the contribution of excess adipose tissue to increased circulating HGF levels in obesity. Serum HGF was measured by ELISA before and after weight loss due to bariatric surgery or a 24-h fast. At 6.1 ± 0.1 mo following surgery, BMI (50.6 ± 1.6 vs. 35.1 ± 1.3 kg/m2; P < 0.0001) and serum HGF were significantly decreased (1,164 ± 116 vs. 529 ± 39 pg/ml, P < 0.001). A 24-h fast did not change serum HGF, but serum leptin was significantly reduced (67.7 ± 7.1 vs. 50.3 ± 8.3 ng/ml, P = 0.02). HGF secretion in vitro from adipocytes of obese (BMI 40.3 ± 2.8 kg/m2) subjects was significantly greater (80.9 ± 10.4 vs. 21.5 ± 4.0 pg/105 cells, P = 0.008) than release from adipocytes of lean (BMI 23.3 ± 1.4 kg/m2) subjects. HGF mRNA levels determined by real-time RT-PCR were not different in adipocytes from lean (BMI 24.0 ± 0.8 kg/m2) and obese (45.7 ± 3.0 kg/m2) subjects, but serum HGF was significantly elevated in the obese individuals studied (787 ± 61 vs. 489 ± 49 pg/ml, P = 0.001). TNF-α (24 h treatment) significantly increased HGF release from subcutaneous adipocytes 23.6 ± 8.3% over control ( P = 0.02). These data suggest that elevated serum HGF in obesity is in part attributable to excess adipose tissue and that this effect can be reversed by reducing adipose tissue mass through weight loss. Increased HGF secretion from adipocytes of obese subjects may be due to posttranscriptional events possibly related to adipocyte size and stimulation by elevated TNF-α in the adipose tissue of obese individuals.

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Adult rats prenatally exposed to ethanol have increased gluconeogenesis and impaired insulin response of hepatic gluconeogenic genes

Journal of Applied Physiology ◽

10.1152/japplphysiol.01115.2005 ◽

2006 ◽

Vol 100 (2) ◽

pp. 642-648 ◽

Cited By ~ 40

Author(s):

Xing-Hai Yao ◽

Li Chen ◽

B. L. Grégoire Nyomba

Keyword(s):

Insulin Response ◽

Insulin Injection ◽

Peroxisome Proliferator ◽

Mrna Levels ◽

Adult Rats ◽

Peroxisome Proliferator Activated Receptor ◽

Insulin Resistant ◽

Adult Rat ◽

Rat Offspring ◽

Before And After

Rat offspring exposed to ethanol (EtOH rats) during pregnancy are insulin resistant, but it is unknown whether they have increased gluconeogenesis. To address this issue, we determined blood glucose and liver gluconeogenic genes, proteins, and enzyme activities before and after insulin administration in juvenile and adult EtOH rats and submitted adult EtOH rats to a pyruvate challenge. In juvenile rats, basal glucose; peroxisome proliferator-activated receptor-coactivator-1α protein and mRNA; and phospho enolpyruvate carboxykinase enzyme activity, protein, and mRNA were similar between groups. After insulin injection, these parameters failed to decrease in EtOH rats, but glucose decreased by 30% and gluconeogenic enzymes, proteins, and mRNAs decreased by 50–70% in control rats. In adult offspring, basal peroxisome proliferator-activated receptor-coactivator-1α protein and mRNA levels were 40–80% higher in EtOH rats than in controls. Similarly, basal phospho enolpyruvate carboxykinase activity, protein, and mRNA were ∼1.8-fold greater in EtOH rats than in controls. These parameters decreased by ∼50% after insulin injection in control rats, but they remained unchanged in EtOH rats. After insulin injection in the adult rats, glucose decreased by 60% in controls but did not decrease significantly in EtOH rats. A subset of adult EtOH rats had fasting hyperglycemia and an exaggerated glycemic response to pyruvate compared with controls. The data indicate that, after prenatal EtOH exposure, the expression of gluconeogenic genes is exaggerated in adult rat offspring and is insulin resistant in both juvenile and adult rats, explaining increased gluconeogenesis. These alterations persist through adulthood and may contribute to the pathogenesis of Type 2 diabetes after exposure to EtOH in utero.

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The Lou/C rat: a model of spontaneous food restriction associated with improved insulin sensitivity and decreased lipid storage in adipose tissue

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90592.2008 ◽

2009 ◽

Vol 296 (5) ◽

pp. E1120-E1132 ◽

Cited By ~ 23

Author(s):

Christelle Veyrat-Durebex ◽

Xavier Montet ◽

Manlio Vinciguerra ◽

Asllan Gjinovci ◽

Paolo Meda ◽

...

Keyword(s):

Adipose Tissue ◽

Lipid Metabolism ◽

Insulin Sensitivity ◽

Insulin Signaling ◽

Food Restriction ◽

Wistar Rats ◽

Uncoupling Protein ◽

Caloric Intake ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor

The inbred Lou/C rat, originating from the Wistar strain, has been described as a model of resistance to diet-induced obesity, but little is known about its metabolism. Since this knowledge could provide some clues about the etiology of obesity/insulin resistance, this study aimed at characterizing glucose and lipid metabolism in Lou/C vs. Wistar rats. This was achieved by performing glucose and insulin tolerance tests, euglycemic hyperinsulinemic clamps, and characterization of intracellular insulin signaling in skeletal muscle. Substrate-induced insulin secretion was evaluated using perfused pancreas and isolated islets. Finally, body fat composition and the expression of various factors involved in lipid metabolism were determined. Body weight and caloric intake were lower in Lou/C than in Wistar rats, whereas food efficiency was similar. Improved glucose tolerance of Lou/C rats was not related to increased insulin output but was related to improved insulin sensitivity/responsiveness in the liver and in skeletal muscles. In the latter tissue, this was accompanied by improved insulin signaling, as suggested by higher activation of the insulin receptor and of the Akt/protein kinase B pathway. Fat deposition was markedly lower in Lou/C than in Wistar rats, especially in visceral adipose tissue. In the inguinal adipose depot, expression of uncoupling protein-1 was detected in Lou/C but not in Wistar rats, in keeping with a higher expression of peroxisome proliferator-activated receptor-γ coactivator-1 in these animals. The Lou/C rat is a valuable model of spontaneous food restriction with associated improved insulin sensitivity. Independently from its reduced caloric intake, it also exhibits a preferential channeling of nutrients toward utilization rather than storage.

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Depot-specific characteristics of adipose tissue-derived stromal cells in thyroid-associated orbitopathy

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2017-311339 ◽

2018 ◽

Vol 102 (8) ◽

pp. 1173-1178 ◽

Cited By ~ 1

Author(s):

Janice Siu Chong Wong ◽

Wai Kit Chu ◽

Benjamin Fuk-Loi Li ◽

Chi-Pui Pang ◽

Kelvin Kam-lung Chong

Keyword(s):

Adipose Tissue ◽

Stromal Cells ◽

Smooth Muscle Actin ◽

Mrna Level ◽

Nile Red ◽

Immunofluorescent Staining ◽

Peroxisome Proliferator ◽

Mrna Levels ◽

Peroxisome Proliferator Activated Receptor ◽

Reverse Transcription Pcr

BackgroundThyroid-associated orbitopathy (TAO) causes inflammatory fibroproliferation of periocular connective tissues. We compared adipose tissue-derived stem/stromal cells (ADSCs) from three adipose depots of each patient with TAO on mesenchymal, myofibrogenic, adipogenic properties and associated hyaluronan (HA) synthesis.MethodsADSCs were generated from periocular (eyelid, orbital) and subcutaneous (abdominal) adipose tissues of three patients with TAO. Mesenchymal markers were characterised by reverse transcription-PCR and immunofluorescent staining. A 3-week adipogenic induction was evaluated by Nile red staining and quantitative PCR (qPCR) of peroxisome proliferator-activated receptor (PPARγ), adiponectin and hyaluronan synthase (HAS)-2. A 7-day myofibrogenic induction was assayed by immunofluorescent staining and qPCR of α-smooth muscle actin (α-SMA).ResultsADSCs from all depots expressed similar levels of mesenchymal markers CD44, CD90 and CD105 (p=0.288, p=0.43 and p=0.837, respectively). After adipogenic induction, intracellular lipid increased for more than 32% and PPARγ mRNA showed more than twofold increase from all three depots. However, adiponectin and HAS-2 mRNA levels were significantly higher in the eyelid and orbital ADSCs than those from the subcutaneous ADSCs after induction (2.4×107, 3.9×106 folds vs below detection limit; 63.3-fold, 26.1-fold, vs 33% reduction, respectively; all p=0.002). Significantly more myofibroblasts and higher mRNA level of α-SMA were obtained from the orbital and eyelid compared with the subcutaneous ADSCs during myofibrogenic induction (80.2%, 70.6% vs 29.3%; 30.2-fold, 24.2-fold vs 1.7-fold, respectively; all p=0.002).ConclusionADSCs from different adipose depots of the same donors exhibited similar mesenchymal phenotypes but differed significantly in adipogenic, myofibrogenic potentials and associated HA synthesis. These depot-specific characteristics of ADSCs may contribute to site-specific adipose tissue involvement in TAO.

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Depot- and sex-specific effects of maternal obesity in offspring’s adipose tissue

Journal of Endocrinology ◽

10.1530/joe-16-0037 ◽

2016 ◽

Vol 230 (1) ◽

pp. 39-53 ◽

Cited By ~ 41

Author(s):

Simon Lecoutre ◽

Barbara Deracinois ◽

Christine Laborie ◽

Delphine Eberlé ◽

Céline Guinez ◽

...

Keyword(s):

Adipose Tissue ◽

Fatty Acid Synthase ◽

Maternal Obesity ◽

Female Offspring ◽

Male Offspring ◽

Peroxisome Proliferator ◽

Mrna Levels ◽

Rapid Weight Gain ◽

Peroxisome Proliferator Activated Receptor ◽

Accelerated Growth

According to the Developmental Origin of Health and Disease (DOHaD) concept, alterations of nutrient supply in the fetus or neonate result in long-term programming of individual body weight (BW) setpoint. In particular, maternal obesity, excessive nutrition, and accelerated growth in neonates have been shown to sensitize offspring to obesity. The white adipose tissue may represent a prime target of metabolic programming induced by maternal obesity. In order to unravel the underlying mechanisms, we have developed a rat model of maternal obesity using a high-fat (HF) diet (containing 60% lipids) before and during gestation and lactation. At birth, newborns from obese dams (called HF) were normotrophs. However, HF neonates exhibited a rapid weight gain during lactation, a key period of adipose tissue development in rodents. In males, increased BW at weaning (+30%) persists until 3months of age. Nine-month-old HF male offspring was normoglycemic but showed mild glucose intolerance, hyperinsulinemia, and hypercorticosteronemia. Despite no difference in BW and energy intake, HF adult male offspring was predisposed to fat accumulation showing increased visceral (gonadal and perirenal) depots weights and hyperleptinemia. However, only perirenal adipose tissue depot exhibited marked adipocyte hypertrophy and hyperplasia with elevated lipogenic (i.e. sterol-regulated element binding protein 1 (Srebp1), fatty acid synthase (Fas), and leptin) and diminished adipogenic (i.e. peroxisome proliferator-activated receptor gamma (Pparγ), 11β-hydroxysteroid dehydrogenase type 1 (11β-Hds1)) mRNA levels. By contrast, very few metabolic variations were observed in HF female offspring. Thus, maternal obesity and accelerated growth during lactation program offspring for higher adiposity via transcriptional alterations of visceral adipose tissue in a depot- and sex-specific manner.

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