Effects of age, gender, and senescence on β-adrenergic responses of isolated F344 rat brown adipocytes in vitro

1998 ◽  
Vol 274 (4) ◽  
pp. E726-E736 ◽  
Author(s):  
Annette M. Gabaldón ◽  
Roger B. McDonald ◽  
Barbara A. Horwitz
Keyword(s):  
Uncoupling Protein ◽  
Physiological State ◽  
Gender Effects ◽  
Rapid Weight Loss ◽  
Brown Adipocytes ◽  
Cl 316,243 ◽  
Age Related ◽  
Brown Adipose ◽  
Camp Levels

We previously reported greater age-related attenuation of cold-induced thermoregulation and brown adipose tissue thermogenic capacity in male vs. female F344 rats. With onset of the rapid weight loss that occurs near the end of the lifespan, this age-related attenuation becomes severe. We refer to this “end-of-life” physiological state of older rats as senescence. Here, we measured oxygen consumption of isolated brown adipocytes and found no age (6 vs. 12 vs. 26 mo) or gender effects on maximal norepinephrine (NE)- or CL-316,243 (β3-adrenergic agonist)-induced responses. In contrast, brown adipocytes from 22- to 26-mo-old senescent rats (males and females) consumed 51–60% less oxygen during maximal stimulation with NE and CL-316,243 than did cells from 26-mo-old presenescent rats. This attenuation was associated with lower (65–72%) uncoupling protein 1 concentrations but no alterations in NE-induced cAMP levels or lipolysis. Our data indicate that senescence, but not chronological age, significantly impacts NE-/β3-mediated thermogenesis of isolated brown adipocytes and that this effect involves altered mitochondrial rather than altered membrane or cytosol events.

scholarly journals ASKA technology-based pull-down method reveals a suppressive effect of ASK1 on the inflammatory NOD-RIPK2 pathway in brown adipocytes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Saki Takayanagi ◽  
Kengo Watanabe ◽  
Takeshi Maruyama ◽  
Motoyuki Ogawa ◽  
Kazuhiro Morishita ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Biological Significance ◽  
Suppressive Effect ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
Adipose Tissues ◽  
Signaling Complex ◽  
Brown Adipose ◽  
Immune Pathway

AbstractRecent studies have shown that adipose tissue is an immunological organ. While inflammation in energy-storing white adipose tissues has been the focus of intense research, the regulatory mechanisms of inflammation in heat-producing brown adipose tissues remain largely unknown. We previously identified apoptosis signal-regulating kinase 1 (ASK1) as a critical regulator of brown adipocyte maturation; the PKA-ASK1-p38 axis facilitates uncoupling protein 1 (UCP1) induction cell-autonomously. Here, we show that ASK1 suppresses an innate immune pathway and contributes to maintenance of brown adipocytes. We report a novel chemical pull-down method for endogenous kinases using analog sensitive kinase allele (ASKA) technology and identify an ASK1 interactor in brown adipocytes, receptor-interacting serine/threonine-protein kinase 2 (RIPK2). ASK1 disrupts the RIPK2 signaling complex and inhibits the NOD-RIPK2 pathway to downregulate the production of inflammatory cytokines. As a potential biological significance, an in vitro model for intercellular regulation suggests that ASK1 facilitates the expression of UCP1 through the suppression of inflammatory cytokine production. In parallel to our previous report on the PKA-ASK1-p38 axis, our work raises the possibility of an auxiliary role of ASK1 in brown adipocyte maintenance through neutralizing the thermogenesis-suppressive effect of the NOD-RIPK2 pathway.

scholarly journals Selective loss of the uncoupling protein from light versus heavy mitochondria of brown adipocytes after a decrease in noradrenergic stimulation in vivo and in vitro

1995 ◽  
Vol 311 (1) ◽  
pp. 327-331 ◽  
Author(s):  
M L Bonet ◽  
F Serra ◽  
J C Matamala ◽  
F J García-Palmer ◽  
A Palou
Keyword(s):  
Uncoupling Protein ◽  
Adrenergic Stimulation ◽  
Fat Cell ◽  
Brown Adipocytes ◽  
Selective Loss ◽  
Mitochondrial Fractions ◽  
Brown Adipose ◽  
Undifferentiated Cells

The relative stability against a decrease in adrenergic stimulation of the uncoupling protein (UCP) incorporated into different mitochondrial fractions was investigated in brown-fat-cell cultures. Cultures were initiated with undifferentiated cells from young mice and were acutely stimulated with noradrenaline at confluence (day 7). Cells were harvested just after the finish of the 24 h stimulation treatment or 24 h later, and three mitochondrial fractions were isolated by differential centrifugation: the M1 fraction (1000 g), the M3 fraction (3000 g) and the M15 fraction (15,000 g). The results obtained in vitro indicate that removal of adrenergic stimulation determines a selective loss of UCP from the lightest mitochondrial fractions (M3 and M15). Similar results were obtained in a situation in vivo (24 h starvation in mice) which is known to lead to a decreased noradrenaline input to brown adipose tissue, with decreased UCP levels. Thus brown adipocytes possess different mitochondrial subpopulations, which exhibit characteristic changes in their UCP turnover in response to thermogenic signals.

scholarly journals TAF7L modulates brown adipose tissue formation

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Haiying Zhou ◽  
Bo Wan ◽  
Ivan Grubisic ◽  
Tommy Kaplan ◽  
Robert Tjian
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Core Promoter ◽  
Uncoupling Protein ◽  
Dna Looping ◽  
Chromatin Interactions ◽  
Brown Adipose ◽  
Important Regulator

Brown adipose tissue (BAT) plays an essential role in metabolic homeostasis by dissipating energy via thermogenesis through uncoupling protein 1 (UCP1). Previously, we reported that the TATA-binding protein associated factor 7L (TAF7L) is an important regulator of white adipose tissue (WAT) differentiation. In this study, we show that TAF7L also serves as a molecular switch between brown fat and muscle lineages in vivo and in vitro. In adipose tissue, TAF7L-containing TFIID complexes associate with PPARγ to mediate DNA looping between distal enhancers and core promoter elements. Our findings suggest that the presence of the tissue-specific TAF7L subunit in TFIID functions to promote long-range chromatin interactions during BAT lineage specification.

Hypoxic Stress Upregulates the Expression of Slc38a1 in Brown Adipocytes via Hypoxia-Inducible Factor-1α

Pharmacology ◽  
2017 ◽  
Vol 101 (1-2) ◽  
pp. 64-71 ◽  
Author(s):  
Tetsuhiro Horie ◽  
Kazuya Fukasawa ◽  
Takashi Iezaki ◽  
Gyujin Park ◽  
Yuki Onishi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Hypoxia Inducible Factor ◽  
Amino Acid Transporters ◽  
Hypoxic Stress ◽  
Gene Encoding ◽  
Brown Adipocytes ◽  
Hypoxia Inducible Factor 1Α ◽  
Brown Adipose

The availability of amino acid in the brown adipose tissue (BAT) has been shown to be altered under various conditions; however, little is known about the possible expression and pivotal role of amino acid transporters in BAT under physiological and pathological conditions. The present study comprehensively investigated whether amino acid transporters are regulated by obesogenic conditions in BAT in vivo. Moreover, we investigated the mechanism underlying the regulation of the expression of amino acid transporters by various stressors in brown adipocytes in vitro. The expression of solute carrier family 38 member 1 (Slc38a1; gene encoding sodium-coupled neutral amino acid transporter 1) was preferentially upregulated in the BAT of both genetic and acquired obesity mice in vivo. Moreover, the expression of Slc38a1 was induced by hypoxic stress through hypoxia-inducible factor-1α, which is a master transcription factor of the adaptive response to hypoxic stress, in brown adipocytes in vitro. These results indicate that Slc38a1 is an obesity-associated gene in BAT and a hypoxia-responsive gene in brown adipocytes.

scholarly journals Regulation of cold-induced thermogenesis by the RNA binding protein FAM195A

2021 ◽  
Vol 118 (23) ◽  
pp. e2104650118
Author(s):  
Jessica Cannavino ◽  
Mengle Shao ◽  
Yu A. An ◽  
Svetlana Bezprozvannaya ◽  
Shiuhwei Chen ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Uncoupling Protein ◽  
Rna Binding Protein ◽  
Cold Environments ◽  
Transport Chain ◽  
Brown Adipose ◽  
Mitochondrial Oxidation ◽  
Branched Chain

Homeothermic vertebrates produce heat in cold environments through thermogenesis, in which brown adipose tissue (BAT) increases mitochondrial oxidation along with uncoupling of the electron transport chain and activation of uncoupling protein 1 (UCP1). Although the transcription factors regulating the expression of UCP1 and nutrient oxidation genes have been extensively studied, only a few other proteins essential for BAT function have been identified. We describe the discovery of FAM195A, a BAT-enriched RNA binding protein, which is required for cold-dependent thermogenesis in mice. FAM195A knockout (KO) mice display whitening of BAT and an inability to thermoregulate. In BAT of FAM195A KO mice, enzymes involved in branched-chain amino acid (BCAA) metabolism are down-regulated, impairing their response to cold. Knockdown of FAM195A in brown adipocytes in vitro also impairs expression of leucine oxidation enzymes, revealing FAM195A to be a regulator of BCAA metabolism and a potential target for metabolic disorders.

scholarly journals Exposure to the Widely Used Pyrethroid Pesticide Deltamethrin, Does Not Exacerbate High Fat Diet Induced Obesity or Insulin Resistance in C57BL/6J Mice

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A45-A46
Author(s):  
Evangelia Evelyn Tsakiridis ◽  
Marisa Morrow ◽  
Andrea Llanos ◽  
Bo Wang ◽  
Alison Holloway ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glycemic Control ◽  
Metabolic Diseases ◽  
Uncoupling Protein ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
Pyrethroid Pesticide ◽  
First Time

Abstract Deltamethrin is a commonly used pesticide for the control of mosquito populations. Despite widespread use, the effects of deltamethrin on adiposity and glucose homeostasis have been equivocal with some studies showing increased, decreased and no effect on adiposity and glycemic control. However, no study to date has investigated the effect of deltamethrin in mice housed at thermoneutral temperatures, which is important for modelling metabolic diseases in rodents due to reduced thermal stress and constitutive activation of brown adipose tissue. In the current study we demonstrate for the first time that deltamethrin reduces uncoupling protein-1 expression in brown adipocytes cultured in vitro at concentrations as low as 1pm. Meanwhile, in-vivo deltamethrin does not appear to alter glycemic control or promote adiposity at exposures equivalent to 0.01, 0.1 or 1.0 mg/kg/day. Together, our study demonstrates environmentally relevant exposure to deltamethrin does not exacerbate diet induced obesity or insulin resistance.

scholarly journals Dopamine directly increases mitochondrial mass and thermogenesis in brown adipocytes

2017 ◽  
Vol 58 (2) ◽  
pp. 57-66 ◽  
Author(s):  
Rose Kohlie ◽  
Nina Perwitz ◽  
Julia Resch ◽  
Sebastian M Schmid ◽  
Hendrik Lehnert ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Energy Homeostasis ◽  
Uncoupling Protein ◽  
Brown Adipocyte ◽  
Peroxisome Proliferator ◽  
Cellular Mechanisms ◽  
Brown Adipocytes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitochondrial Mass ◽  
Brown Adipose

Brown adipose tissue (BAT) is key to energy homeostasis. By virtue of its thermogenic potential, it may dissipate excessive energy, regulate body weight and increase insulin sensitivity. Catecholamines are critically involved in the regulation of BAT thermogenesis, yet research has focussed on the effects of noradrenaline and adrenaline. Some evidence suggests a role of dopamine (DA) in BAT thermogenesis, but the cellular mechanisms involved have not been addressed. We employed our extensively characterised murine brown adipocyte cells. D1-like and D2-like receptors were detectable at the protein level. Stimulation with DA caused an increase in cAMP concentrations. Oxygen consumption rates (OCR), mitochondrial membrane potential (Δψm) and uncoupling protein 1 (UCP1) levels increased after 24 h of treatment with either DA or a D1-like specific receptor agonist. A D1-like receptor antagonist abolished the DA-mediated effect on OCR, Δψm and UCP1. DA induced the release of fatty acids, which did not additionally alter DA-mediated increases of OCR. Mitochondrial mass (as determined by (i) CCCP- and oligomycin-mediated effects on OCR and (ii) immunoblot analysis of mitochondrial proteins) also increased within 24 h. This was accompanied by an increase in peroxisome proliferator-activated receptor gamma co-activator 1 alpha protein levels. Also, DA caused an increase in p38 MAPK phosphorylation and pharmacological inhibition of p38 MAPK abolished the DA-mediated effect on Δψm. In summary, our study is the first to reveal direct D1-like receptor and p38 MAPK-mediated increases of thermogenesis and mitochondrial mass in brown adipocytes. These results expand our understanding of catecholaminergic effects on BAT thermogenesis.

cAMP metabolism and lipolysis in brown adipocytes of hamsters consuming a cafeteria diet

1985 ◽  
Vol 248 (2) ◽  
pp. E224-E229
Author(s):  
R. J. Schimmel ◽  
L. McCarthy ◽  
K. K. McMahon
Keyword(s):  
Adenylate Cyclase ◽  
Sympathetic Activity ◽  
Brown Fat ◽  
Adenylate Cyclase System ◽  
Brown Adipocytes ◽  
Beta Adrenergic ◽  
Fat Depots ◽  
Brown Adipose ◽  
Camp Levels ◽  
In Cells

Feeding animals cafeteria diets causes increased sympathetic activity to brown adipose tissue and this is believed to be responsible for the concomitant activation of thermogenesis. Because chronic catecholamine stimulation in other systems leads to a desensitization of beta-adrenergic receptors, we examined lipolysis and cAMP production in brown adipocytes of hamsters eating cafeteria diets for evidence of diminished beta-adrenergic responses. Basal cAMP levels were similar in chow- and cafeteria-fed hamsters. However, adipocytes from overfed animals formed less cAMP in response to isoproterenol than those of control animals. Isoproterenol-stimulated adenylate cyclase activity was similarly decreased in membrane preparations from cafeteria-fed hamsters. However, when the diterpene forskolin was used, equal amounts of cAMP were formed in cells and membrane preparations from control and overfed animals. In contrast to the reduced responses of the cAMP system to isoproterenol stimulation observed in overfed hamsters, isoproterenol-stimulated lipolysis was greater in cells from overfed animals than in cells from control animals. These results are consistent with a desensitization of the adenylate cyclase system in brown adipocytes occurring during chronic hyperphagia. Because eating cafeteria diets has been reported to increase sympathetic activity to brown fat depots, the apparent desensitization of brown adipocytes observed in this study may result from a persistent stimulation of the brown fat with norepinephrine in vivo. Our data also suggest the existence of mechanisms that preserve lipolysis in the face of low cAMP levels.

scholarly journals SUN-587 IDH1-Dependent Alpha-KG Regulates Brown Fat Differentiation and Function by Modulating Histone Methylation

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Won Kon Kim ◽  
Baek-Soo Han
Keyword(s):  
Histone Methylation ◽  
Molecular Mechanisms ◽  
Adipocyte Differentiation ◽  
Uncoupling Protein ◽  
Ectopic Expression ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
Brown Adipose ◽  
And Function ◽  
Brown Adipogenesis

Abstract Brown adipocytes play important roles in the regulation of energy homeostasis by uncoupling protein 1-mediated non-shivering thermogenesis. Recent studies suggest that brown adipocytes as novel therapeutic targets for combating obesity and associated diseases, such as type II diabetes. However, the molecular mechanisms underlying brown adipocyte differentiation and function are not fully understood. We employed previous findings obtained through proteomic studies performed to assess proteins displaying altered levels during brown adipocyte differentiation. Here, we performed assays to determine the functional significance of their altered levels during brown adipogenesis and development. We identified isocitrate dehydrogenase 1 (IDH1) as upregulated during brown adipocyte differentiation, with subsequent investigations revealing that ectopic expression of IDH1 inhibited brown adipogenesis, whereas suppression of IDH1 levels promoted differentiation of brown adipocytes. Additionally, Idh1 overexpression resulted in increased levels of intracellular α-ketoglutarate (α-KG) and inhibited the expression of genes involved in brown adipogenesis. Exogenous treatment with α-KG reduced brown adipogenesis during the early phase of differentiation, and ChIP analysis revealed that IDH1-mediated α-KG reduced trimethylation of histone H3 lysine 4 in the promoters of genes associated with brown adipogenesis. Furthermore, administration of α-KG decreased adipogenic gene expression by modulating histone methylation in brown adipose tissues of mice. These results suggested that the IDH1–α-KG axis plays an important role in regulating brown adipocyte differentiation and might represent a therapeutic target for treating metabolic diseases.

scholarly journals In vitro and in vivo induction of brown adipocyte uncoupling protein (thermogenin) by retinoic acid

1996 ◽  
Vol 317 (3) ◽  
pp. 827-833 ◽  
Author(s):  
Pere PUIGSERVER ◽  
Francisca VÁZQUEZ ◽  
María L. BONET ◽  
Catalina PICÓ ◽  
Andreu PALOU
Keyword(s):  
Retinoic Acid ◽  
Cultured Cells ◽  
Uncoupling Protein ◽  
Primary Cultures ◽  
Brown Adipocyte ◽  
Brown Adipose ◽  
Adipocyte Cell ◽  
Differentiation Stage

The effects of retinoic acid (RA) isomers (all-trans-RA and 9-cis-RA) on the appearance of uncoupling protein (UCP; thermogenin), the only unequivocal molecular marker of the brown adipocyte differentiated phenotype, have been investigated in primary cultures of brown adipocytes, in the brown adipocyte cell line HIB 1B and directly in intact mice. The results obtained with cultured cells indicate that retinoids function as inducers of the appearance of UCP and, at the same time, partially inhibit brown adipocyte cell proliferation. The two RA isomers displayed similar effectiveness as UCP inducers, their effect being comparable with that triggered by noradrenaline, so far considered to be the main modulator of UCP gene expression. The effectiveness of retinoids as UCP inducers was dependent on the stage of brown adipocyte differentiation, being maximal in confluent primary cells and in the medium–late differentiation stage of HIB 1B cells. Corroborating the results obtained in vitro, we show that administration of all-trans-RA or 9-cis-RA to mice leads to an increase in their brown adipose tissue specific UCP content. 9-cis-RA treatment also prevented the loss of UCP on cold deacclimation. To our knowledge, this is the first report of a stimulatory effect of retinoid compounds on UCP induction in vivo.

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