Inhibition of lipolysis and lipogenesis in isolated rat adipocytes with AICAR, a cell‐permeable activator of AMP‐activated protein kinase

FEBS Letters

Brocklehurst, Katy J.¹  Marley, Anna E.¹  Carey, Frank¹  Sullivan, Jane E.¹  Carling, David²  Beri, Raj K.¹ 

[1] Cardiovascular and Metabolism Research Department, ZENECA Pharmaceuticals, Alderley Park, Cheshire SK10 4TG, UK;MRC Molecular Medicine Group, Royal Postgraduate Medical School, Ducane Road, London W12 ONN, UK

关键词: AMP-activated protein kinase;    Hormone-sensitive lipase;    Acetyl-CoA carboxylase;    Lipolysis;    Lipogenesis;    Adipocyte (rat);    AMPK;    AMP-activated protein kinase;    AICAR;    5-amino-4-imidazolecarboxamide ribonucleoside;    HSL;    hormone-sensitive lipase;    ACC;    acetyl-CoA carboxylase;    PKA;    cAMP-dependent protein kinase;    OkA;    okadaic acid;   

DOI  :  10.1016/0014-5793(94)01006-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In vivo, hormone-sensitive lipase (HSL) is known to be phosphorylated on two sites termed the regulatory and basal sites. However, the intracellular role of the basal site or the identity of the protein kinase phosphorylating this site has not been established. We show that 5-amino-4-imidazolecarboxamide ribonucleoside (AICAR) markedly activates cellular AMP-activated protein kinase (AMPK) in a time- and dose-dependent manner. As expected for an agent that activates AMPK intracellularly, AICAR had no effect on the basal activity of HSL. However, preincubation of adipocytes with AICAR led to a reduced response of these cells to the lipolytic agent isoprenaline. AICAR was also shown to profoundly inhibit lipogenesis through increased phosphorylation of acetyl-CoA carboxylase (ACC). Thus it appears that in addition to regulating lipogenesis, AMPK also plays an important antilipolytic role by regulating HSL in rat adipocytes.

【 授权许可】

Unknown