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Academy of Scientific and Innovative Research, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India
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Academy of Scientific and Innovative Research, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India
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Academy of Scientific and Innovative Research, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India
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Academy of Scientific and Innovative Research, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India
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. In this study for the first time, we have shown the effects of hyperinsulinemia on differentiated and characterized brown adipocytes. Basal chronic hyperinsulinemia (500pM insulin exposure for 72h) causes insulin resistance in both white and brown
School of Medicine, Mater Research Institute, The Translational Research Institute, Princess Alexandra Hospital, University of Queensland, Herston, Queensland, Australia
School of Medicine, Mater Research Institute, The Translational Research Institute, Princess Alexandra Hospital, University of Queensland, Herston, Queensland, Australia
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School of Medicine, Mater Research Institute, The Translational Research Institute, Princess Alexandra Hospital, University of Queensland, Herston, Queensland, Australia
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School of Medicine, Mater Research Institute, The Translational Research Institute, Princess Alexandra Hospital, University of Queensland, Herston, Queensland, Australia
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School of Medicine, Mater Research Institute, The Translational Research Institute, Princess Alexandra Hospital, University of Queensland, Herston, Queensland, Australia
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School of Medicine, Mater Research Institute, The Translational Research Institute, Princess Alexandra Hospital, University of Queensland, Herston, Queensland, Australia
School of Medicine, Mater Research Institute, The Translational Research Institute, Princess Alexandra Hospital, University of Queensland, Herston, Queensland, Australia
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). The effect of GCs on BAT in humans is unknown. We have investigated the effects of GCs in a model of primary human adipocytes derived from biopsies of supraclavicular brown adipocyte (BA) depots ( Lee et al . 2011 ). The brown preadipocytes
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basal brown adipose phenotype that may be important for the maintenance of normal insulin sensitivity and energy homeostasis ( Yang et al. 2003 ). Moreover, transdifferentiation of white to brown adipocytes has been demonstrated and may offer
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whitening iBAT photomicrographs ( Fig. 7A ) show brown adipocytes that resemble unilocular white adipocytes in the HF diet group (asterisk), characterizing whitening, which contrasts with the multilocular brown adipocytes in the C diet group (black arrow
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Leptin is an important adipocytokine whose main regulative effects on energy metabolism are exerted via activation of signalling pathways in the central nervous system. Another important regulator of energy homeostasis is insulin. The role of direct autocrine leptin effects on adipose tissue and crosstalk with insulin, in particular in the thermogenically active brown adipose tissue, remains unclear. In the present study, we have investigated leptin secretion and interaction with insulin in highly insulin-responsive immortalised mouse brown adipocytes. Leptin was secreted in a differentiation-dependent manner, and acute leptin treatment of mature adipocytes dose- and time-dependently stimulated phosphorylation of STAT3 and MAP kinase. Interestingly, acute pretreatment of fully differentiated brown adipocytes with leptin (100 nM) significantly diminished insulin-induced glucose uptake by approximately 25%. This inhibitory effect was time-dependent and maximal after 60 min of leptin prestimulation. Furthermore, it correlated with a 35% reduction in insulin-stimulated insulin receptor kinase activity after acute leptin pretreatment. Insulin-induced insulin receptor substrate-1 tyrosine phosphorylation and binding to the regulatory subunit p85 of phosphatidylinositol 3-kinase (PI 3-kinase) were diminished by approximately 60% and 40%, respectively. Taken together, this study has demonstrated strong differentiation-dependent leptin secretion in brown adipocytes and PI 3-kinase-mediated negative autocrine effects of this hormone on insulin action. Direct peripheral leptin-insulin crosstalk may play an important role in the regulation of energy homeostasis.
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Ciliary neurotrophic factor (CNTF) plays an important role in regulating neuronal growth. Recently, central anorexigenic effects of this cytokine have been characterized. However, peripheral effects on tissues that actively contribute to the regulation of energy homeostasis have not been described. Here, we report direct potent and selective effects of CNTF on growth factor and metabolic signalling intermediates in mouse brown adipocytes. CNTF stimulates STAT3, MAP kinase, Akt, and p70 S6 kinase. We find that, next to mediating Akt and p70 S6 kinase activation, both phosphatidylinositol 3-kinase and protein kinase C are separately acting, main intermediates for inducing mitogen-activated protein (MAP) kinase activation. On a functional level, CNTF enhances beta3-adrenergic induction of uncoupling protein-1. Thus, these results demonstrate direct effects of CNTF on adipose tissue signalling and metabolism and suggest a novel role for this cytokine in the peripheral regulation of energy homeostasis.
CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain
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CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain
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CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain
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CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain
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CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain
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CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain
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needed; similarly, BAT has been considered to essentially play a role in energy expenditure to support non-shivering thermogenesis. We know that, in brown adipocytes, there is a regulated uncoupling of the mitochondrial respiratory chain relative to ATP
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National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China
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mice underwent metabolic phenotyping and were sacrificed for tissue collection and biochemical study. Primary stromal vascular fractions isolation and differentiation of primary brown adipocytes Stromal vascular fractions (SVFs) from BAT of 2
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. 2016 ), suggestive of increased BAT activity ( Schilperoort et al. 2018 ). In vitro experiments have indicated direct repressing actions of testosterone on BAT activity; one group found that testosterone treatment of brown adipocytes diminished
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responses in white and brown adipocytes respectively. This study demonstrates a direct ACTH-mediated induction of transient insulin resistance, a pro-inflammatory adipokine profile and a p38 mitogen-activated protein kinase (MAPK)-mediated induction of
