A single day of high fat diet feeding induces lipid accumulation and insulin resistance in brown adipose tissue in mice

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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Male and Female Animals Respond Differently to High-Fat Diet and Regular Exercise Training in a Mouse Model of Hyperlipidemia

International Journal of Molecular Sciences ◽

10.3390/ijms22084198 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4198

Author(s):

Melinda E. Tóth ◽

Brigitta Dukay ◽

Mária Péter ◽

Gábor Balogh ◽

Gergő Szűcs ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Lipid Accumulation ◽

High Fat Diet ◽

The Body ◽

Treadmill Running ◽

Cardiometabolic Health ◽

Regular Exercise ◽

High Fat ◽

Brown Adipose

Inappropriate nutrition and a sedentary lifestyle can lead to obesity, one of the most common risk factors for several chronic diseases. Although regular physical exercise is an efficient approach to improve cardiometabolic health, the exact cellular processes are still not fully understood. We aimed to analyze the morphological, gene expression, and lipidomic patterns in the liver and adipose tissues in response to regular exercise. Healthy (wild type on a normal diet) and hyperlipidemic, high-fat diet-fed (HFD-fed) apolipoprotein B-100 (APOB-100)-overexpressing mice were trained by treadmill running for 7 months. The serum concentrations of triglyceride and tumor necrosis factor α (TNFα), as well as the level of lipid accumulation in the liver, were significantly higher in HFD-fed APOB-100 males compared to females. However, regular exercise almost completely abolished lipid accumulation in the liver of hyperlipidemic animals. The expression level of the thermogenesis marker, uncoupling protein-1 (Ucp1), was significantly higher in the subcutaneous white adipose tissue of healthy females, as well as in the brown adipose tissue of HFD-fed APOB-100 females, compared to males. Lipidomic analyses revealed that hyperlipidemia essentially remodeled the lipidome of brown adipose tissue, affecting both the membrane and storage lipid fractions, which was partially restored by exercise in both sexes. Our results revealed more severe metabolic disturbances in HFD-fed APOB-100 males compared to females. However, exercise efficiently reduced the body weight, serum triglyceride levels, expression of pro-inflammatory factors, and hepatic lipid accumulation in our model.

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A single day of high-fat diet feeding induces lipid accumulation and insulin resistance in brown adipose tissue in mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00123.2019 ◽

2019 ◽

Vol 317 (5) ◽

pp. E820-E830 ◽

Cited By ~ 4

Author(s):

Eline N. Kuipers ◽

Ntsiki M. Held ◽

Wietse in het Panhuis ◽

Melanie Modder ◽

Philip M. M. Ruppert ◽

...

Keyword(s):

Insulin Resistance ◽

Fatty Acids ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

High Fat Diet ◽

Mitochondrial Dynamics ◽

Core Body Temperature ◽

High Fat ◽

Rapid Induction ◽

Brown Adipose

Brown adipose tissue (BAT) catabolizes glucose and fatty acids to produce heat and thereby contributes to energy expenditure. Long-term high-fat diet (HFD) feeding results in so-called ‘whitening’ of BAT characterized by increased lipid deposition, mitochondrial dysfunction, and reduced fat oxidation. The aim of the current study was to unravel the rate and related mechanisms by which HFD induces BAT whitening and insulin resistance. Wild-type mice were fed a HFD for 0, 1, 3, or 7 days. Within 1 day of HFD, BAT weight and lipid content were increased. HFD also immediately reduced insulin-stimulated glucose uptake by BAT, indicating rapid induction of insulin resistance. This was accompanied by a tendency toward a reduced uptake of triglyceride-derived fatty acids by BAT. Mitochondrial mass and Ucp1 expression were unaltered, whereas after 3 days of HFD, markers of mitochondrial dynamics suggested induction of a more fused mitochondrial network. Additionally, HFD also increased macrophage markers in BAT after 3 days of HFD. Counterintuitively, the switch to HFD was accompanied by an acute rise in core body temperature. We showed that a single day of HFD feeding is sufficient to induce the first signs of whitening and insulin resistance in BAT, which reduces the uptake of glucose and triglyceride-derived fatty acids. BAT whitening and insulin resistance are likely sustained by reduced mitochondrial oxidation due to changes in mitochondrial dynamics and macrophage infiltration, respectively. Likely, the switch to HFD swiftly induces thermogenesis in other metabolic organs, which allows attenuation of BAT thermogenesis.

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Brown adipose tissue metabolism in ob/ob mice: effects of a high-fat diet and adrenalectomy

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1987.253.2.e149 ◽

1987 ◽

Vol 253 (2) ◽

pp. E149-E157

Author(s):

H. K. Kim ◽

D. R. Romsos

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

High Fat Diet ◽

High Fat ◽

Adipose Tissue Metabolism ◽

High Carbohydrate ◽

Bat Mitochondria ◽

Norepinephrine Turnover ◽

Brown Adipose ◽

Thermogenic Capacity

Adrenalectomy prevents development of obesity in ob/ob mice fed high-carbohydrate stock diets partly by stimulating the low thermogenic capacity of their brown adipose tissue (BAT). Adrenalectomy, however, fails to prevent development of obesity in ob/ob mice fed a high-fat diet. Effects of adrenalectomy on BAT metabolism in ob/ob mice fed a high-fat diet were thus examined. ob/ob mice fed the high-fat diet developed gross obesity despite normal BAT metabolism, as assessed by rates of norepinephrine turnover in BAT, GDP binding to BAT mitochondria, and GDP-inhibitable, chloride-induced mitochondrial swelling. Adrenalectomy failed to arrest the development of obesity or to influence BAT metabolism in ob/ob mice fed the high-fat diet. Development of obesity in ob/ob mice fed a high-fat diet is not associated with low thermogenic capacity of BAT or with adrenal secretions, as it is in ob/ob mice fed high-carbohydrate stock diets.

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The novel non‐steroidal MR antagonist finerenone improves metabolic parameters in high‐fat diet‐fed mice and activates brown adipose tissue via AMPK‐ATGL pathway

The FASEB Journal ◽

10.1096/fj.202000164r ◽

2020 ◽

Vol 34 (9) ◽

pp. 12450-12465 ◽

Cited By ~ 1

Author(s):

Vincenzo Marzolla ◽

Alessandra Feraco ◽

Stefania Gorini ◽

Caterina Mammi ◽

Carmen Marrese ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

High Fat Diet ◽

Metabolic Parameters ◽

The Novel ◽

High Fat ◽

Brown Adipose

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Defective trophic response of brown adipose tissue of myopathic hamsters

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1984.247.6.e800 ◽

1984 ◽

Vol 247 (6) ◽

pp. E800-E807

Author(s):

J. Triandafillou ◽

W. Hellenbrand ◽

J. Himms-Hagen

Keyword(s):

Adipose Tissue ◽

Muscular Dystrophy ◽

Brown Adipose Tissue ◽

Protein Content ◽

High Fat Diet ◽

Marked Reduction ◽

Short Photoperiod ◽

Normal Amount ◽

High Fat ◽

Brown Adipose

Hamsters with muscular dystrophy (BIO 14.6) have a smaller than normal amount of brown adipose tissue. Two stimuli that promote growth of brown adipose tissue in normal hamsters, short photoperiod and eating a high-fat diet, are here shown to be without effect on brown adipose tissue of myopathic hamsters. Cold-induced growth of brown adipose tissue occurs normally [Am. J. Physiol. 239 (Cell Physiol. 8): C18–C22, 1980]. There is a normal rate of turnover of norepinephrine in brown adipose tissue of the myopathic hamster but a failure of the tissue to hypertrophy in response to norepinephrine is unlikely since norepinephrine does not appear to mediate the trophic response [Am. J. Physiol. 247 (Endocrinol. Metab. 10): E793–E799, 1984]. Denervation results in a marked reduction in size (protein content) of brown adipose tissue of normal hamsters but has very little effect on the size of brown adipose tissue of myopathic hamsters. A central, possibly hypothalamic, defect in the myopathic hamster is postulated to underlie its abnormal control of brown adipose tissue hypertrophy.

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Anti-Obesity Effects of Grateloupia elliptica, a Red Seaweed, in Mice with High-Fat Diet-Induced Obesity via Suppression of Adipogenic Factors in White Adipose Tissue and Increased Thermogenic Factors in Brown Adipose Tissue

Nutrients ◽

10.3390/nu12020308 ◽

2020 ◽

Vol 12 (2) ◽

pp. 308 ◽

Cited By ~ 4

Author(s):

Hyo-Geun Lee ◽

Yu An Lu ◽

Xining Li ◽

Ji-Min Hyun ◽

Hyun-Soo Kim ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

White Adipose Tissue ◽

High Fat Diet ◽

Red Seaweed ◽

High Fat ◽

Adipose Tissues ◽

Ppar Γ ◽

Brown Adipose ◽

Treatment Of Obesity

Obesity is a serious metabolic syndrome characterized by high levels of cholesterol, lipids in the blood, and intracellular fat accumulation in adipose tissues. It is known that the suppression of adipogenic protein expression is an effective approach for the treatment of obesity, and regulates fatty acid storage and transportation in adipose tissues. The 60% ethanol extract of Grateloupia elliptica (GEE), a red seaweed from Jeju Island in Korea, was shown to exert anti-adipogenic activity in 3T3-L1 cells and in mice with high-fat diet (HFD)-induced obesity. GEE inhibited intracellular lipid accumulation in 3T3-L1 cells, and significantly reduced expression of adipogenic proteins. In vivo experiments indicated a significant reduction in body weight, as well as white adipose tissue (WAT) weight, including fatty liver, serum triglycerides, total cholesterol, and leptin contents. The expression of the adipogenic proteins, SREBP-1 and PPAR-γ, was significantly decreased by GEE, and the expression of the metabolic regulator protein was increased in WAT. The potential of GEE was shown in WAT, with the downregulation of PPAR-γ and C/EBP-α mRNA; in contrast, in brown adipose tissue (BAT), the thermogenic proteins were increased. Collectively, these research findings suggest the potential of GEE as an effective candidate for the treatment of obesity-related issues via functional foods or pharmaceutical agents.

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Does a high-fat diet-induced obesity model brown adipose tissue thermogenesis? A systematic review

Archives of Medical Science ◽

10.5114/aoms.2019.86781 ◽

2019 ◽

Author(s):

Gabriela S. Perez ◽

Gabriele D.S. Cordeiro ◽

Lucimeire S. Santos ◽

Djane D.A. Espírito-Santo ◽

Gilson T. Boaventura ◽

...

Keyword(s):

Systematic Review ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

High Fat Diet ◽

High Fat ◽

Diet Induced Obesity ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis

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Diet, lighting, and food intake affect norepinephrine turnover in dietary obesity

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1987.252.2.r402 ◽

1987 ◽

Vol 252 (2) ◽

pp. R402-R408 ◽

Cited By ~ 2

Author(s):

T. Yoshida ◽

J. S. Fisler ◽

M. Fukushima ◽

G. A. Bray ◽

R. A. Schemmel

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

High Fat Diet ◽

Brown Fat ◽

Light Cycle ◽

High Fat ◽

Interscapular Brown Adipose Tissue ◽

Norepinephrine Turnover ◽

Brown Adipose ◽

Dietary Obesity

The effects of dietary fat content, lighting cycle, and feeding time on norepinephrine turnover in interscapular brown adipose tissue, heart, and pancreas, and on blood 3-hydroxybutyrate, serum glucose, insulin, and corticosterone have been studied in two strains of rats that differ in their susceptibility to dietary obesity. S 5B/Pl rats, which are resistant to dietary obesity, have a more rapid turnover of norepinephrine in interscapular brown adipose tissue and heart and a greater increase in the concentration of norepinephrine in brown fat when eating a high-fat diet than do Osborne-Mendel rats, which are sensitive to fat-induced obesity. Light cycle and feeding schedule are important modulators of sympathetic activity in heart and pancreas but not in brown fat. Rats of the resistant strain also have higher blood 3-hydroxybutyrate concentrations and lower insulin and corticosterone levels than do rats of the susceptible strain. A high-fat diet increases 3-hydroxybutyrate concentrations and reduces insulin levels in both strains. These studies show, in rats eating a high-fat diet, that differences in norepinephrine turnover, particularly in brown adipose tissue, may play an important role in whether dietary obesity develops and in the manifestations of resistance to this phenomenon observed in the S 5B/Pl rat.

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