Dataset Information

Acute stimulation of white adipocyte respiration by PKA-induced lipolysis.

ABSTRACT:

Objective

We examined the effect of ?-adrenergic receptor (?AR) activation and cAMP-elevating agents on respiration and mitochondrial uncoupling in human adipocytes and probed the underlying molecular mechanisms.

Research design and methods

Oxygen consumption rate (OCR, aerobic respiration) and extracellular acidification rate (ECAR, anaerobic respiration) were examined in response to isoproterenol (ISO), forskolin (FSK), and dibutyryl-cAMP (DB), coupled with measurements of mitochondrial depolarization, lipolysis, kinase activities, and gene targeting or knock-down approaches.

Results

ISO, FSK, or DB rapidly increased oxidative and glycolytic respiration together with mitochondrial depolarization in human and mouse white adipocytes. The increase in OCR was oligomycin-insensitive and contingent on cAMP-dependent protein kinase A (PKA)-induced lipolysis. This increased respiration and the uncoupling were blocked by inhibiting the mitochondrial permeability transition pore (PTP) and its regulator, BAX. Interestingly, compared with lean individuals, adipocytes from obese subjects exhibited reduced OCR and uncoupling capacity in response to ISO.

Conclusions

Lipolysis stimulated by ?AR activation or other maneuvers that increase cAMP levels in white adipocytes acutely induces mitochondrial uncoupling and cellular energetics, which are amplified in the absence of scavenging BSA. The increase in OCR is dependent on PKA-induced lipolysis and is mediated by the PTP and BAX. Because this effect is reduced with obesity, further exploration of this uncoupling mechanism will be needed to determine its cause and consequences.

SUBMITTER: Yehuda-Shnaidman E

PROVIDER: S-EPMC3279548 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Publications

Acute stimulation of white adipocyte respiration by PKA-induced lipolysis.

Yehuda-Shnaidman Einav E Buehrer Ben B Pi Jingbo J Kumar Naresh N Collins Sheila S

Diabetes 20100803 10

<h4>Objective</h4>We examined the effect of β-adrenergic receptor (βAR) activation and cAMP-elevating agents on respiration and mitochondrial uncoupling in human adipocytes and probed the underlying molecular mechanisms.<h4>Research design and methods</h4>Oxygen consumption rate (OCR, aerobic respiration) and extracellular acidification rate (ECAR, anaerobic respiration) were examined in response to isoproterenol (ISO), forskolin (FSK), and dibutyryl-cAMP (DB), coupled with measurements of mitoc ...[more]

PMID: 20682684

Similar Datasets

Project description:Gut-derived short-chain fatty acids (SCFA), formed by microbial fermentation of dietary fibers, are believed to be involved in the etiology of obesity and diabetes. Previous data from our group showed that colonic infusions of physiologically relevant SCFA mixtures attenuated whole-body lipolysis in overweight men. To further study potential mechanisms involved in the antilipolytic properties of SCFA, we aimed to investigate the in vitro effects of SCFA incubations on intracellular lipolysis and signaling using a human white adipocyte model, the human multipotent adipose tissue-derived stem (hMADS) cells.hMADS adipocytes were incubated with mixtures of acetate, propionate, and butyrate or single SCFA (acetate, propionate and butyrate) in concentrations ranging between 1?µmol/L and 1?mmol/L. Glycerol release and lipase activation was investigated during basal conditions and following ?-adrenergic stimulation.SCFA mixtures high in acetate and propionate decreased basal glycerol release, when compared to control (P?<?0.05), while mixtures high in butyrate had no effect. Also, ?-adrenergic receptor mediated glycerol release was not significantly altered following incubation with SCFA mixtures. Incubation with only acetate decreased basal (1?µmol/L) and ?-adrenergically (1?µmol/L and 1?mmol/L) mediated glycerol release when compared with control (P?<?0.05). In contrast, butyrate (1?µmol/L) slightly increased basal and ?-adrenergically mediated glycerol release compared with control (P?<?0.05), while propionate had no effect on lipolysis. The antilipolytic effect of acetate was accompanied by a reduced phosphorylation of hormone-sensitive lipase (HSL) at serine residue 650. In addition, inhibition of Gi G proteins following pertussis toxin treatment prevented the antilipolytic effect of acetate.The present data demonstrated that acetate was mainly responsible for the antilipolytic effects of SCFA and acts via attenuation of HSL phosphorylation in a Gi-coupled manner in hMADS adipocytes. Therefore, the modulation of colonic and circulating acetate may be an important target to modulate human adipose tissue lipid metabolism.

Dataset Information

Acute stimulation of white adipocyte respiration by PKA-induced lipolysis.

Objective

Research design and methods

Results

Conclusions

Publications

Acute stimulation of white adipocyte respiration by PKA-induced lipolysis.

Similar Datasets

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