Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism.
Dysregulation of lipid metabolism in individual tissues leads to systemic disruption of insulin action and glucose metabolism. Utilizing quantitative lipidomic analyses and mice deficient in adipose tissue lipid chaperones aP2 and mal1, we explored how metabolic alterations in adipose tissue are linked to whole-body metabolism through lipid signals. A robust increase in de novo lipogenesis rendered the adipose tissue of these mice resistant to the deleterious effects of dietary lipid exposure. Systemic lipid profiling also led to identification of C16:1n7-palmitoleate as an adipose tissue-derived lipid hormone that strongly stimulates muscle insulin action and suppresses hepatosteatosis. Our data reveal a lipid-mediated endocrine network and demonstrate that adipose tissue uses lipokines such as C16:1n7-palmitoleate to communicate with distant organs and regulate systemic metabolic homeostasis.
Cao
Haiming
H
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Gerhold
Kristin
K
Mayers
Jared R
JR
Wiest
Michelle M
MM
Watkins
Steven M
SM
Hotamisligil
Gökhan S
GS
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D050218:Body Fat Distribution; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000032:analysis* / Q000097:blood / Q000378:metabolism; D006728:Hormones / Q000032:analysis*; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism; D050155:Lipogenesis; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism
C493411:Fabp4 protein, mouse; C082667:Fabp5 protein, mouse; D050556:Fatty Acid-Binding Proteins; D005229:Fatty Acids, Monounsaturated; D006728:Hormones; D007328:Insulin; D009363:Neoplasm Proteins; C008757:palmitoleic acid; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase