Limonoid 7-Deacetoxy-7-oxogedunin from Andiroba, Carapa guianensis, Meliaceae, Decreased Body Weight Gain, Improved Insulin Sensitivity, and Activated Brown Adipose Tissue in High-Fat-Diet-Fed Mice

Our previous study reported that lactic acid bacteria (L. brevis OPK-3) isolated from kimchi ameliorated intracellular lipid accumulation in 3T3-L1 adipocyte. The current study explored potential roles of L. brevis OPK-3 (KLAB) on preventing body weight gain and its effect on the inflammatory response of adipose tissue. Male C57BL/6 mice (n = 10) were divided into four groups: normal diet with distilled water (NDC), high-fat diet with distilled water (HDC), high-fat diet with L-ornithine (OTC) or high-fat diet with KLAB. The KLAB supplement resulted in significantly lower body weight, lower epididymal fat tissue mass, and lower serum and hepatic TG levels than the HDC. KLAB supplementation improved serum cytokines, and real-time polymerase chain reaction (PCR) analysis showed significantly lower inflammatory cytokine mRNA levels in epididymal adipose tissue. These results suggest that the administration of KLAB inhibits the induction of inflammation in adipose tissue along with the inhibition of weight gain. Therefore, this study demonstrates the therapeutic and beneficial value of this strain produced during the fermentation of kimchi.

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Increased sensitivity of the genetically obese mouse to corticosterone

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1987.252.2.e202 ◽

1987 ◽

Vol 252 (2) ◽

pp. E202-E208 ◽

Cited By ~ 2

Author(s):

K. Tokuyama ◽

J. Himms-Hagen

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Food Intake ◽

Brown Adipose Tissue ◽

Body Weight Gain ◽

Serum Insulin ◽

Obese Mouse ◽

Serum Corticosterone ◽

Brown Adipose

Adrenalectomy normalizes many abnormalities of the obese (ob/ob) mouse. The high corticosterone concentration in blood may account in part for development of obesity and other abnormalities in the ob/ob mouse. Our objective was to determine dose-response relationships for the effect of corticosterone on the obesity. Lean and ob/ob mice were adrenalectomized or sham-operated at 4.5 wk of age. Adrenalectomized mice received 100 mg implants of cholesterol containing corticosterone (0, 2, 5, 20, or 50 mg) at 8.5 wk of age and were killed at 10.5 wk of age. In ob/ob mice, but not in lean mice, low physiological levels of serum corticosterone (up to 10 micrograms/dl) markedly increased body weight gain, food intake, and serum insulin. They also increased white and brown adipose tissue weights and decreased brown adipose tissue mitochondrial GDP binding. Higher levels of corticosterone (12-22 micrograms/dl) increased body weight gain, white and brown adipose tissue weights, and serum insulin and suppressed brown adipose tissue mitochondrial GDP binding in lean mice also, although in most cases to a lesser extent than in ob/ob mice, but were still without effect on food intake. Only very high levels of corticosterone (approximately 30 micrograms/dl) increased food intake in lean mice. Hyperglycemia was induced in ob/ob, but not lean, mice only at concentrations of corticosterone greater than 17 micrograms/dl. Thermoregulation was unaffected by serum corticosterone at levels from 0 to 30 micrograms/dl in both ob/ob and lean mice. Thus the ob/ob mouse is excessively sensitive and responsive to an effect of physiological levels of corticosterone that results in hyperphagia, hyperinsulinemia, and increased weight gain.(ABSTRACT TRUNCATED AT 250 WORDS)

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Haploinsufficiency of the retinoblastoma protein gene reduces diet-induced obesity, insulin resistance, and hepatosteatosis in mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00163.2009 ◽

2009 ◽

Vol 297 (1) ◽

pp. E184-E193 ◽

Cited By ~ 29

Author(s):

Josep Mercader ◽

Joan Ribot ◽

Incoronata Murano ◽

Søren Feddersen ◽

Saverio Cinti ◽

...

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

High Fat Diet ◽

Retinoblastoma Protein ◽

Brown Adipocyte ◽

Wild Type ◽

High Fat ◽

Brown Adipose

Brown adipose tissue activity dissipates energy as heat, and there is evidence that lack of the retinoblastoma protein (pRb) may favor the development of the brown adipocyte phenotype in adipose cells. In this work we assessed the impact of germ line haploinsufficiency of the pRb gene (Rb) on the response to high-fat diet feeding in mice. Rb+/− mice had body weight and adiposity indistinguishable from that of wild-type (Rb+/+) littermates when maintained on a standard diet, yet they gained less body weight and body fat after long-term high-fat diet feeding coupled with reduced feed efficiency and increased rectal temperature. Rb haploinsufficiency ameliorated insulin resistance and hepatosteatosis after high-fat diet in male mice, in which these disturbances were more marked than in females. Compared with wild-type littermates, Rb+/− mice fed a high-fat diet displayed higher expression of peroxisome proliferator-activated receptor (PPAR)γ as well as of genes involved in mitochondrial function, cAMP sensitivity, brown adipocyte determination, and tissue vascularization in white adipose tissue depots. Furthermore, Rb+/− mice exhibited signs of enhanced activation of brown adipose tissue and higher expression levels of PPARα in liver and of PPARδ in skeletal muscle, suggestive of an increased capability for fatty acid oxidation in these tissues. These findings support a role for pRb in modulating whole body energy metabolism and the plasticity of the adipose tissues in vivo and constitute first evidence that partial deficiency in the Rb gene protects against the development of obesity and associated metabolic disturbances.

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Ellagic Acid Affects Metabolic and Transcriptomic Profiles and Attenuates Features of Metabolic Syndrome in Adult Male Rats

Nutrients ◽

10.3390/nu13030804 ◽

2021 ◽

Vol 13 (3) ◽

pp. 804

Author(s):

Adéla Kábelová ◽

Hana Malínská ◽

Irena Marková ◽

Olena Oliyarnyk ◽

Blanka Chylíková ◽

...

Keyword(s):

Oxidative Stress ◽

Metabolic Syndrome ◽

Body Weight ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Ellagic Acid ◽

High Fat Diet ◽

Male Rats ◽

High Fat ◽

Brown Adipose

Ellagic acid, a natural substance found in various fruits and nuts, was previously shown to exhibit beneficial effects towards metabolic syndrome. In this study, using a genetic rat model of metabolic syndrome, we aimed to further specify metabolic and transcriptomic responses to ellagic acid treatment. Adult male rats of the SHR-Zbtb16Lx/k.o. strain were fed a high-fat diet accompanied by daily intragastric gavage of ellagic acid (50 mg/kg body weight; high-fat diet–ellagic acid (HFD-EA) rats) or vehicle only (high-fat diet–control (HFD-CTL) rats). Morphometric and metabolic parameters, along with transcriptomic profile of liver and brown and epididymal adipose tissues, were assessed. HFD-EA rats showed higher relative weight of brown adipose tissue (BAT) and decreased weight of epididymal adipose tissue, although no change in total body weight was observed. Glucose area under the curve, serum insulin, and cholesterol levels, as well as the level of oxidative stress, were significantly lower in HFD-EA rats. The most differentially expressed transcripts reflecting the shift induced by ellagic acid were detected in BAT, showing downregulation of BAT activation markers Dio2 and Nr4a1 and upregulation of insulin-sensitizing gene Pla2g2a. Ellagic acid may provide a useful nutritional supplement to ameliorate features of metabolic syndrome, possibly by suppressing oxidative stress and its effects on brown adipose tissue.

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Energy balance and brown adipose tissue thermogenesis during chronic endotoxemia in rats

Journal of Applied Physiology ◽

10.1152/jappl.1989.66.4.1970 ◽

1989 ◽

Vol 66 (4) ◽

pp. 1970-1975 ◽

Cited By ~ 5

Author(s):

J. Arnold ◽

R. A. Little ◽

N. J. Rothwell

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Energy Balance ◽

Energy Expenditure ◽

Brown Adipose Tissue ◽

Body Weight Gain ◽

Male Rats ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis

The effects of continuously administered endotoxin on 7-day energy balance were investigated in male rats. Three groups of rats were implanted with osmotic pumps; two groups received saline-filled pumps, whereas the third received endotoxin. One of the saline groups was pair fed to match the food intake of the endotoxemic rats. After 7 days, body energy and protein and fat contents of rats were determined together with the energy content of food and feces. Endotoxin infusion not only induced fever, but it also suppressed appetite and significantly decreased body weight gain. Metabolizable energy intake was reduced by approximately 20% in infected rats. Although protein and fat gains were lowest in the endotoxin group, there appeared to be a selective loss of protein when considered as percent of body weight. Percent body fat was unaltered between the groups. Energy expenditure considered in absolute (kJ) or body weight-independent (kJ/kg0.67) terms yielded similar patterns of results; expenditure (kJ) was 10 and 20% (P less than 0.05, P less than 0.01) lower in the endotoxemic and pair-fed rats, respectively, compared with controls. Hence, compared with pair-fed rats, endotoxin-infused animals had a 10% rise in their expenditure. Brown adipose tissue thermogenesis was assessed by mitochondrial binding of guanosine 5′-diphosphate, and results showed that binding was greatest in endotoxemic rats and lowest in the pair-fed animals. The present results suggest that in this endotoxemic model appetite suppression exacerbates changes in energy balance. However, the reduction in body weight gain is also dependent on a decrease in metabolic efficiency and an increase in total energy expenditure.(ABSTRACT TRUNCATED AT 250 WORDS)

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Inactivation of SPAK kinase reduces body weight gain in mice fed a high-fat diet by improving energy expenditure and insulin sensitivity

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00108.2017 ◽

2018 ◽

Vol 314 (1) ◽

pp. E53-E65 ◽

Cited By ~ 8

Author(s):

Ivan Torre-Villalvazo ◽

Luz Graciela Cervantes-Pérez ◽

Lilia G. Noriega ◽

Jose V. Jiménez ◽

Norma Uribe ◽

...

Keyword(s):

Adipose Tissue ◽

Weight Gain ◽

Insulin Sensitivity ◽

Energy Expenditure ◽

Glucose Tolerance ◽

High Fat Diet ◽

Whole Body ◽

High Fat ◽

The Metabolic Syndrome ◽

Brown Adipose

The STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) controls the activity of the electroneutral cation-chloride cotransporters (SLC12 family) and thus physiological processes such as modulation of cell volume, intracellular chloride concentration [Cl−]i, and transepithelial salt transport. Modulation of SPAK kinase activity may have an impact on hypertension and obesity, as STK39, the gene encoding SPAK, has been suggested as a hypertension and obesity susceptibility gene. In fact, the absence of SPAK activity in mice in which the activating threonine in the T loop was substituted by alanine (SPAK-KI mice) is associated with decreased blood pressure; however its consequences in metabolism have not been explored. Here, we fed wild-type and homozygous SPAK-KI mice a high-fat diet for 17 wk to evaluate weight gain, circulating substrates and hormones, energy expenditure, glucose tolerance, and insulin sensitivity. SPAK-KI mice exhibit resistance to HFD-induced obesity and hepatic steatosis associated with increased energy expenditure, higher thermogenic activity in brown adipose tissue, increased mitochondrial activity in skeletal muscle, and reduced white adipose tissue hypertrophy mediated by augmented whole body insulin sensitivity and glucose tolerance. Our data reveal a previously unrecognized role for the SPAK kinase in the regulation of energy balance, thermogenesis, and insulin sensitivity, suggesting that this kinase could be a new drug target for the treatment of obesity and the metabolic syndrome.

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Cranberry Polyphenolic Extract Exhibits an Antiobesity Effect on High-Fat Diet–Fed Mice through Increased Thermogenesis

Journal of Nutrition ◽

10.1093/jn/nxaa163 ◽

2020 ◽

Vol 150 (8) ◽

pp. 2131-2138 ◽

Cited By ~ 1

Author(s):

Fang Zhou ◽

Jielong Guo ◽

Xue Han ◽

Yunxiao Gao ◽

Qimin Chen ◽

...

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

High Fat Diet ◽

Body Weight Gain ◽

Uncoupling Protein ◽

The Body ◽

High Fat ◽

Uncoupling Protein 1 ◽

Polyphenolic Extract ◽

Brown Adipose

ABSTRACT Background Although polyphenol-rich cranberry extracts reportedly have an antiobesity effect, the exact reason for this remains unclear. Objectives In light of the reported health benefits of the polyphenolic compounds in cranberry, we investigated the effects and mechanism of a cranberry polyphenolic extract (CPE) in high-fat diet (HFD)–fed obese mice. Methods The distributions of individual CPE compounds were characterized by HPLC fingerprinting. Male C57BL/6J mice (4 wk old) were fed for 16 wk normal diet (ND, 10% fat energy) or HFD (60% fat energy) with or without 0.75% CPE in drinking water (HFD + CPE). Body and adipose depot weights, indices of glucose metabolism, energy expenditure (EE), and expression of genes related to brown adipose tissue (BAT) thermogenesis, and inguinal/epididymal white adipose tissue (iWAT/eWAT) browning were measured. Results After 16 wk, the body weight was 22.5% lower in the CPE-treated mice than in the HFD group but remained 17.9% higher than in the ND group. CPE treatment significantly increased EE compared with that of the ND and HFD groups. The elevated EE was linked with BAT thermogenesis, and iWAT/eWAT browning, shown by the induction of thermogenic genes, especially uncoupling protein 1 (Ucp1), and browning-related genes, including Cd137, a member of the tumor necrosis factor receptor superfamily (Tnfrsf9). The mRNA expression and abundance of uncoupling protein 1 in BAT of CPE-fed mice were 5.78 and 1.47 times higher than in the HFD group, and 0.61 and 1.12 times higher than in the ND group, respectively. Cd137 gene expression in iWAT and eWAT of CPE-fed mice were 2.35 and 3.13 times higher than in the HFD group, and 0.84 and 1.39 times higher than in the ND group, respectively. Conclusions Dietary CPE reduced but did not normalize HFD-induced body weight gain in male C57BL/6J mice, possibly by affecting energy metabolism.

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