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

Yehuda-Shnaidman E, Buehrer B, Pi J, Kumar N, Collins S
Diabetes. 2010 59 (10): 2474-83

PMID: 20682684 · PMCID: PMC3279548 · DOI:10.2337/db10-0245

OBJECTIVE - 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.

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 βAR 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.

MeSH Terms (21)

Adipocytes, White Aerobiosis Anaerobiosis Animals Bucladesine Colforsin Cyclic AMP Humans Ion Channels Isoproterenol Isoquinolines Male Mice Mice, Knockout Mitochondrial Proteins Oxygen Consumption Protein Kinase Inhibitors Reverse Transcriptase Polymerase Chain Reaction RNA, Small Interfering Sulfonamides Uncoupling Protein 2

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