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Switching harmful visceral fat to beneficial energy combustion improves metabolic dysfunctions.

ABSTRACT: Visceral fat is considered the genuine and harmful white adipose tissue (WAT) that is associated to development of metabolic disorders, cardiovascular disease, and cancer. Here, we present a new concept to turn the harmful visceral fat into a beneficial energy consumption depot, which is beneficial for improvement of metabolic dysfunctions in obese mice. We show that low temperature-dependent browning of visceral fat caused decreased adipose weight, total body weight, and body mass index, despite increased food intake. In high-fat diet-fed mice, low temperature exposure improved browning of visceral fat, global metabolism via nonshivering thermogenesis, insulin sensitivity, and hepatic steatosis. Genome-wide expression profiling showed upregulation of WAT browning-related genes including Cidea and Dio2. Conversely, Prdm16 was unchanged in healthy mice or was downregulated in obese mice. Surgical removal of visceral fat and genetic knockdown of UCP1 in epididymal fat largely ablated low temperature-increased global thermogenesis and resulted in the death of most mice. Thus, browning of visceral fat may be a compensatory heating mechanism that could provide a novel therapeutic strategy for treating visceral fat-associated obesity and diabetes.

SUBMITTER: Yang X

PROVIDER: S-EPMC5313060 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Switching harmful visceral fat to beneficial energy combustion improves metabolic dysfunctions.

Yang Xiaoyan X Sui Wenhai W Zhang Meng M Dong Mei M Lim Sharon S Seki Takahiro T Guo Ziheng Z Fischer Carina C Lu Huixia H Zhang Cheng C Yang Jianmin J Zhang Meng M Wang Yangang Y Cao Caixia C Gao Yanyan Y Zhao Xingguo X Sun Meili M Sun Yuping Y Zhuang Rujie R Samani Nilesh J NJ Zhang Yun Y Cao Yihai Y

JCI insight 20170223 4

Visceral fat is considered the genuine and harmful white adipose tissue (WAT) that is associated to development of metabolic disorders, cardiovascular disease, and cancer. Here, we present a new concept to turn the harmful visceral fat into a beneficial energy consumption depot, which is beneficial for improvement of metabolic dysfunctions in obese mice. We show that low temperature-dependent browning of visceral fat caused decreased adipose weight, total body weight, and body mass index, despit ...[more]

PMID: 28239649

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Project description:Smallanthus sonchifolius (yacon), a native plant of South America, was observed to improve lipid profile in rodents and humans. This study aimed to investigate the antiobesity properties of yacon roots in a high-fat-diet (HFD) model and the underlying mechanisms. A total of 30 Wistar male rats were divided into five groups (n=6): the standard chow diet (SD) group was fed a SD; the HFD group was fed a HFD; and the HFD Y340 and HFD Y680 groups were fed a HFD plus yacon flour (340 and 680 mg FOS/kg b. w./day, respectively). HFD Y340 and HFD Y680 rats exhibited marked attenuation of weight gain, a decrease in visceral fat pad weight, a restoration of the serum lipid profile and atherogenic index in a dose-dependent manner, being the higher dose more effective (p < 0.05). In addition, we found that HFD Y680 rats showed lower glucose and insulin levels, improved glucose tolerance, and insulin sensitivity (p < 0.5). A downregulation of several adipocyte specific-transcription factors, including peroxisome proliferator-activated receptor gamma2 (PPAR-γ2), CCAAT/enhancer binding protein a (C/EBP-a) and activating protein (aP2) mRNA levels, was determined in the visceral adipose tissue of HFD Y680 rats (p < 0.05). An improvement of adipokine profile in HFD Y680 rats and decreased serum proinflammatory cytokine levels (p < 0.05) were determined by ELISA. Decreased macrophage infiltration and F4/80 and MCP-1 expression in the visceral adipose tissue of HFD Y680 rats (p < 0.5), together with a higher pAkt/Akt expression (p < 0.05) were also observed by immunofluorescence and immunoblotting. A significant increase in glucagon (Gcg) and PYY mRNA levels in distal ileum of HFD Y680 rats (p < 0.05) were also detected. In the second approach, we determined that yacon supplementation potentiates the effects of the HFD reversion to a standard diet. In conclusion, yacon showed antiobesity properties by inhibiting adipogenesis and improving the visceral adipose tissue function.

Project description:ObjectiveMetformin is known to have a beneficial effect on body weight and body composition, although the precise mechanism has not been elucidated yet. The aim of this study is to investigate the effects of metformin on energy metabolism and anthropometric factors in both human subjects and rats.MethodsIn human studies, metformin (1500mg/day) was administered to 23 healthy subjects and 18 patients with type 2 diabetes for 2 weeks. Metabolic parameters and energy metabolism were measured during a meal tolerance test in the morning before and after the treatment of metformin. In animal studies, 13 weeks old SD rats were fed 25-26 g of standard chow only during 12-hours dark phase with either treated by metformin (2.5mg/ml in drinking water) or not for 2 weeks, and metabolic parameters, anthropometric factors and energy metabolism together with expressions related to fat oxidation and adaptive thermogenesis were measured either in fasting or post-prandial state at 15 weeks old.ResultsPost-prandial plasma lactate concentration was significantly increased after the metformin treatment in both healthy subjects and diabetic patients. Although energy expenditure (EE) did not change, baseline respiratory quotient (RQ) was significantly decreased and post-prandial RQ was significantly increased vice versa following the metformin treatment in both groups. By the administration of metformin to SD rats for 2 weeks, plasma levels of lactate and pyruvate were significantly increased in both fasting and post-prandial states. RQ during a fasting state was significantly decreased in metformin-treated rats compared to controls with no effect on EE. Metformin treatment brought about a significant reduction of visceral fat mass compared to controls accompanied by an up-regulation of fat oxidation-related enzyme in the liver, UCP-1 in the brown adipose tissue and UCP-3 in the skeletal muscle.ConclusionFrom the results obtained, beneficial effects of metformin on visceral fat reduction has been demonstrated probably through a mechanism for a potential shift of fuel resource into fat oxidation and an upregulation of adaptive thermogenesis independent of an anorexigenic effect of this drug.

Project description:ObjectiveThis study assessed longitudinal changes in body composition, fat distribution and energy balance in perimenopausal women. We hypothesized that total fat and abdominal body fat would increase at menopause due to decreased energy expenditure (EE) and declining estrogen, respectively.DesignObservational, longitudinal study with annual measurements for 4 years.SubjectsHealthy women (103 Caucasian; 53 African-American), initially premenopausal. During follow-up, lack of menstruation for 1 year and follicle-stimulating hormone >30 mIU ml(-1) defined a subject as postmenopausal.MeasurementsFat and lean mass (dual-energy X-ray absorptiometry), visceral (VAT) and subcutaneous abdominal fat (SAT) (computed tomography), dietary intake (4-day food record), serum sex hormones and physical activity (tri-axial accelerometry). Twenty-four hour EE was measured by whole-room calorimeter in a subset of 34 women at baseline and at year 4.ResultsBody fat and weight increased significantly over time only in those women who became postmenopausal by year 4 (n=51). All women gained SAT over time; however, only those who became postmenopausal had a significant increase in VAT. The postmenopausal group also exhibited a significant decrease in serum estradiol. Physical activity decreased significantly 2 years before menopause and remained low. Dietary energy, protein, carbohydrate and fiber intake were significantly higher 3-4 years before the onset of menopause compared with menopause onset. Twenty-four hour EE and sleeping EE decreased significantly with age; however, the decrease in sleeping EE was 1.5-fold greater in women who became postmenopausal compared with premenopausal controls (-7.9 vs -5.3%). Fat oxidation decreased by 32% in women who became postmenopausal (P<0.05), but did not change in those who remained premenopausal.ConclusionMiddle-aged women gained SAT with age, whereas menopause per se was associated with an increase in total body fat and VAT. Menopause onset is associated with decreased EE and fat oxidation that can predispose to obesity if lifestyle changes are not made.

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Switching harmful visceral fat to beneficial energy combustion improves metabolic dysfunctions.

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Switching harmful visceral fat to beneficial energy combustion improves metabolic dysfunctions.

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