Increased FGF21 in brown adipose tissue of tyrosine hydroxylase heterozygous mice: implications for cold adaptation

Vázquez, Patricia; Hernández‐Sánchez, Catalina; Escalona-Garrido, Carmen; Pereira, Leonel; Contreras, Cristina; López, Miguel; Balsinde, Jesús; Pablo, Flora de; Valverde, Ángela M.

doi:10.1194/jlr.m085209

Cited by 8 publications

(6 citation statements)

References 62 publications

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“…It has been found that FGF21 can enhance energy consumption by regulating the expression of thermogenic genes in adipose tissues such as BAT and subcutaneous WAT, thus reducing blood glucose and lipid levels and ameliorating glucose tolerance and insulin resistance in obese and diabetic mice [ 109–111 ]. Under long-term cold exposure, FGF21 expression in both BAT and subcutaneous WAT of mice increased significantly [ 112 , 113 ]. Under cold exposure conditions, FGF21 significantly enhances PGC-1α protein levels, and enables PGC-1α to participate in thermogenesis of adipose tissue induced by FGF21 [ 114 ].…”

Section: Fibroblast Growth Factor 21mentioning

confidence: 99%

Brown and beige adipose tissue: a novel therapeutic strategy for obesity and type 2 diabetes mellitus

et al. 2021

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Section: Fibroblast Growth Factor 21mentioning

confidence: 99%

Brown and beige adipose tissue: a novel therapeutic strategy for obesity and type 2 diabetes mellitus

et al. 2021

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“…The liver and the AT secrete it in endocrine, paracrine and autocrine ways. Fgf21 is a crucial gene in BAT activation and browning of WAT [ 42 , 43 ]. It stimulates PPAR-γ activity and PGC1-α expression, and enhances UCP1 production, increasing the thermogenic activity in beige and brown cells [ 42 , 44 , 45 ].…”

Section: Thermogenic Adipose Tissuementioning

confidence: 99%

“…FGF21 and adiponectin are two identified molecules with an atheroprotective behavior released by activated BAT ( Figure 3 ), and their potential systemic and local anti-atherogenic effects have been suggested [ 110 ]. FGF21, in addition to its thermogenic implication in beige and brown cells, has several metabolic functions [ 42 , 43 ]. It stimulates PPAR-γ activity and adiponectin expression, increases lipid and glucose uptake and improves lipid profile by suppressing the nuclear sterol regulatory element binding protein-1, a hepatic factor involved in the biosynthesis of cholesterol [ 111 ]; in particular it leads to a decrease of triglyceride and LDL levels and an increase of HDL levels [ 97 , 111 ].…”

Section: Atherosclerosismentioning

confidence: 99%

Browning of White Adipose Tissue as a Therapeutic Tool in the Fight against Atherosclerosis

2021

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Despite continuous medical advances, atherosclerosis remains the prime cause of mortality worldwide. Emerging findings on brown and beige adipocytes highlighted that these fat cells share the specific ability of non-shivering thermogenesis due to the expression of uncoupling protein 1. Brown fat is established during embryogenesis, and beige cells emerge from white adipose tissue exposed to specific stimuli like cold exposure into a process called browning. The consecutive energy expenditure of both thermogenic adipose tissues has shown therapeutic potential in metabolic disorders like obesity and diabetes. The latest data suggest promising effects on atherosclerosis development as well. Upon cold exposure, mice and humans have a physiological increase in brown adipose tissue activation and browning of white adipocytes is promoted. The use of drugs like β3-adrenergic agonists in murine models induces similar effects. With respect to atheroprotection, thermogenic adipose tissue activation has beneficial outcomes in mice by decreasing plasma triglycerides, total cholesterol and low-density lipoproteins, by increasing high-density lipoproteins, and by inducing secretion of atheroprotective adipokines. Atheroprotective effects involve an unaffected hepatic clearance. Latest clinical data tend to find thinner atherosclerotic lesions in patients with higher brown adipose tissue activity. Strategies for preserving healthy arteries are a major concern for public health.

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“…Administration of FGF21 lowered plasma triglycerides in mice through reduced hepatic very low-density lipoprotein secretion and increased lipoprotein disposal in adipose tissue (Schlein et al 2016). FGF21 and PRDM16 have been reported to compensate for the reduced sympathetic response to cold exposure in a tyrosine hydroxylase haplodeficient mouse model suggesting a mechanism independent of the classic adrenergic pathway (Vazquez et al 2018). In humans, circulating FGF21 correlated with brown fat activity determined by FDG uptake in PET/CT studies and in human brown adipocytes FGF21 and FNDC5 had additive effects on norepinephrine-stimulated thermogenesis (Lee et al 2014a, Hanssen et al 2015a.…”

Section: Exercise and Browningmentioning

confidence: 99%

Adipose tissue browning in mice and humans

Herz

Kiefer

2019

Journal of Endocrinology

108

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In the midst of an obesity epidemic, the promotion of brown adipose tissue (BAT) function and the browning of white adipose tissue (WAT) have emerged as promising therapeutic targets to increase energy expenditure and counteract weight gain. Despite the fact that the thermogenic potential of bone fide BAT in rodents is several orders of magnitudes higher than white fat containing brite/beige adipocytes, WAT browning represents a particularly intriguing concept in humans given the extreme amount of excess WAT in obese individuals. In addition, the clear distinction between classic brown and beige fat that has been proposed in mice does not exist in humans. In fact, studies of human BAT biopsies found controversial results suggesting both classic brown and beige characteristics. Irrespective of the true ‘color’, accumulating evidence suggests the induction of thermogenic adipocytes in human WAT depots in response to specific stimuli, highlighting that WAT browning may occur in both, mice and humans. These observations also emphasize the great plasticity of human fat depots and raise important questions about the metabolic properties of thermogenically active adipose tissue in humans and the potential therapeutic implications. We will first review the cellular and molecular aspects of selected adipose tissue browning concepts that have been identified in mouse models with emphasis on neuronal factors, the microbiome, immune cells and several hormones. We will also summarize the evidence for adipose tissue browning in humans including some experimental pharmacologic approaches.

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Increased FGF21 in brown adipose tissue of tyrosine hydroxylase heterozygous mice: implications for cold adaptation

Abstract: are likely due to compensatory mechanisms involving elevations in Fgf21 and Prdm16 and through adaptive changes in the lipid profile.-Vázquez, P.

Cited by 8 publications

References 62 publications

Brown and beige adipose tissue: a novel therapeutic strategy for obesity and type 2 diabetes mellitus

Brown and beige adipose tissue: a novel therapeutic strategy for obesity and type 2 diabetes mellitus

Browning of White Adipose Tissue as a Therapeutic Tool in the Fight against Atherosclerosis

Adipose tissue browning in mice and humans

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