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Thrifty metabolism that favors fat storage after caloric restriction: a role for skeletal muscle phosphatidylinositol-3-kinase activity and AMP-activated protein kinase

journal contribution
posted on 01.03.2008, 00:00 authored by S Summermatter, D Mainieri, Aaron RussellAaron Russell, J Montani, J Seydoux, A Buchala, G Solinas, A Dulloo
Energy conservation directed at accelerating body fat recovery (or catch-up fat) contributes to obesity relapse after slimming and to excess fat gain during catch-up growth after malnutrition. To investigate the mechanisms underlying such thrifty metabolism for catch-up fat, we tested whether during refeeding after caloric restriction rats exhibiting catch-up fat driven by suppressed thermogenesis have diminished skeletal muscle phosphatidylinositol-3-kinase (PI3K) activity or AMP-activated protein kinase (AMPK) signaling—two pathways required for hormone-induced thermogenesis in ex vivo muscle preparations. The results show that during isocaloric refeeding with a low-fat diet, at time points when body fat, circulating free fatty acids, and intramyocellular lipids in refed animals do not exceed those of controls, muscle insulin receptor substrate 1-associated PI3K activity (basal and in vivo insulin-stimulated) is lower than that in controls. Isocaloric refeeding with a high-fat diet, which exacerbates the suppression of thermogenesis, results in further reductions in muscle PI3K activity and in impaired AMPK phosphorylation (basal and in vivo leptin-stimulated). It is proposed that reduced skeletal muscle PI3K/AMPK signaling and suppressed thermogenesis are interdependent. Defective PI3K or AMPK signaling will reduce the rate of substrate cycling between de novo lipogenesis and lipid oxidation, leading to suppressed thermogenesis, which accelerates body fat recovery and furthermore sensitizes skeletal muscle to dietary fat-induced impairments in PI3K/AMPK signaling.—Summermatter, S., Mainieri, D., Russell, A. P., Seydoux, J., Montani, J. P., Buchala, A., Solinas, G., Dulloo, A. G. Thrifty metabolism that favors fat storage after caloric restriction: a role for skeletal muscle phosphatidylinositol-3-kinase activity and AMP-activated protein kinase.

History

Journal

The FASEB journal : official publication of the Federation of American Societies for experimental biology

Volume

22

Issue

3

Pagination

774 - 785

Publisher

Federation of American Societies for Experimental Biology

Location

[Bethesda, Md.]

ISSN

0892-6638

eISSN

1530-6860

Language

eng

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2008, FASEB