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AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons

Claret, M; Smith, MA; Batterham, RL; Selman, C; Choudhury, AI; Fryer, LGD; Clements, M; ... Withers, DJ; + view all (2007) AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons. J CLIN INVEST , 117 (8) 2325 - 2336. 10.1172/JCI31516. Green open access

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Abstract

Hypothalamic AMP-activated protein kinase (AMPK) has been suggested to act as a key sensing mechanism, responding to hormones and nutrients in the regulation of energy homeostasis. However, the precise neuronal populations and cellular mechanisms involved are unclear. The effects of long-term manipulation of hypothalamic AMPK on energy balance are also unknown. To directly address such issues, we generated POMC alpha 2KO and AgRP alpha 2KO mice lacking AMPK alpha 2 in proopiomelanocortin- (POMC-) and agouti-related protein-expressing (AgRP-expressing) neurons, key regulators of energy homeostasis. POMC alpha 2KO mice developed obesity due to reduced energy expenditure and dysregulated food intake but remained sensitive to leptin. in contrast, AgRPa2KO mice developed an age-dependent lean phenotype with increased sensitivity to a melanocortin agonist. Electrophysiological studies in AMPK alpha 2-deficient POMC or AgRP neurons revealed normal leptin or insulin action but absent responses to alterations in extracellular glucose levels, showing that glucose-sensing signaling mechanisms in these neurons are distinct from those pathways utilized by leptin or insulin. Taken together with the divergent phenotypes of POMC alpha 2KO and AgRP alpha 2KO mice, our findings suggest that while AMPK plays a key role in hypothalamic function, it does not act as a general sensor and integrator of energy homeostasis in the mediobasal hypothalamus.

Type: Article
Title: AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons
Open access status: An open access version is available from UCL Discovery
DOI: 10.1172/JCI31516
Publisher version: http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC19345...
Keywords: ACTIVATED PROTEIN-KINASE, HYPOTHALAMIC ARCUATE NUCLEUS, DIABETES-OBESITY SYNDROMES, FATTY-ACID OXIDATION, FOOD-INTAKE, CATALYTIC SUBUNIT, UPSTREAM KINASE, SKELETAL-MUSCLE, NERVOUS-SYSTEM, INSULIN
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/7922
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