Macrophage-derived AIM is endocytosed into adipocytes and decreases lipid droplets via inhibition of fatty acid synthase activity.
Macrophages infiltrate adipose tissue in obesity and are involved in the induction of inflammation, thereby contributing to the development of obesity-associated metabolic disorders. Here, we show that the macrophage-derived soluble protein AIM is endocytosed into adipocytes via CD36. Within adipocytes, AIM associates with cytosolic fatty acid synthase (FAS), thereby decreasing FAS activity. This decreases lipid droplet size, stimulating the efflux of free fatty acids and glycerol from adipocytes. As an additional consequence of FAS inhibition, AIM prevents preadipocyte maturation. In vivo, the increase in adipocyte size and fat weight induced by high-fat diet (HFD) was accelerated in AIM-deficient (AIM(-)(/-)) mice compared to AIM(+/+) mice. Moreover, injection of recombinant AIM in AIM(-)(/-) mice suppresses the increase in fat mass induced by HFD. Interestingly, metabolic rates are comparable in AIM(-)(/-) and AIM(+/+) mice, suggesting that AIM specifically influences adipocyte status. Thus, this AIM function in adipocytes may be physiologically relevant to obesity progression.
Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.
Jun
J
Kurokawa
Satoko
S
Arai
Katsuhiko
K
Nakashima
Hiromichi
H
Nagano
Akemi
A
Nishijima
Keishi
K
Miyata
Rui
R
Ose
Mayumi
M
Mori
Naoto
N
Kubota
Takashi
T
Kadowaki
Yuichi
Y
Oike
Hisashi
H
Koga
Maria
M
Febbraio
Toshihiko
T
Iwanaga
Toru
T
Miyazaki
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D018955:CD36 Antigens / Q000378:metabolism; D004041:Dietary Fats; D004705:Endocytosis; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050356:Lipid Metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D051116:Receptors, Scavenger; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
D051017:Apoptosis Regulatory Proteins; D018955:CD36 Antigens; C117272:Cd5l protein, mouse; D004041:Dietary Fats; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D011994:Recombinant Proteins; D064429:Fatty Acid Synthases