Brown adipose tissue activation is linked to distinct systemic effects on lipid metabolism in humans

Authors: CHONDRONIKOLA, MARIA - Shriners Hospital For Children; VOLPI, ELENA - University Of Texas Medical Branch; BORSHEIM, ELISABET - Arkansas Children'S Nutrition Research Center (ACNC); PORTER, CRAIG - University Of Athens; SARAF, MANISH - Shriners Hospital For Children; ANNAMALAI, PALAM - University Of Texas Medical Branch; YFANTI, CHRISTINA - Shriners Hospital For Children; CHAO, TONY - University Of Texas Medical Branch; WONG, DANIEL - University Of California; SHINODA, KOSAKU - University Of California; LABBE, SEBASTIEN - Quebec Heart And Lung Research Institute; HURREN, NICHOLAS - Shriners Hospital For Children; CESANI, FERNARDO - University Of Texas Medical Branch; KAJIMURA, SHINGO - University Of California; SIDOSSIS, LABROS - Shriners Hospital For Children

Submitted to: Cell Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/28/2016
Publication Date: 5/26/2016
Citation: Chondronikola, M., Volpi, E., Borsheim, E., Porter, C., Saraf, M.K., Annamalai, P., Yfanti, C., Chao, T., Wong, D., Shinoda, K., Labbe, S.M., Hurren, N.M., Cesani, F., Kajimura, S., Sidossis, L.S. 2016. Brown adipose tissue activation is linked to distinct systemic effects on lipid metabolism in humans. Cell Metabolism. 23:1200-1206.

Interpretive Summary: Brown adipose tissue (BAT) is a specialized fat tissue that is most abundant in human neonates and is believed to contribute significantly to regulation of thermogenesis (heat production) during this critical period of development. The importance of BAT in terms of fuel metabolism and impact on whole-body metabolism remains to be fully elaborated. Adult humans have recently been shown to also have BAT, opening the door for clinical research to determine the roles of BAT in normal physiology and pathophysiology. Although rodent studies strongly support a role for BAT in fat metabolism, the significance of BAT in regulation of fat metabolism in humans remains unknown. We studied overweight/obese men during prolonged, mild cold exposure (CE; an activator of BAT thermogenesis) and during thermoneutral (TN) conditions using stable isotopic tracers to measures various pathways, in conjunction with hyperinsulinemic-euglycemic clamps and adipose tissue biopsies. Our results support the notion that BAT volume is associated with increased turnover and oxidation (usage for energy) of fatty acids. Our data support a physiologically important role for BAT in fat handling in humans. By studying BAT metabolism in adults, it sheds light on the potential function of this tissue in human infants. Furthermore, studies may be conducted to determine BAT's role in fat metabolism and other pathways in response to changes in diet, physical activity/exercise, and obesity.

Technical Abstract: Recent studies suggest that brown adipose tissue (BAT) plays a role in energy and glucose metabolism in humans. However, the physiological significance of human BAT in lipid metabolism remains unknown. We studied 16 overweight/obese men during prolonged, non-shivering cold and thermoneutral conditions using stable isotopic tracer methodologies in conjunction with hyperinsulinemic-euglycemic clamps and BAT and white adipose tissue (WAT) biopsies. BAT volume was significantly associated with increased whole-body lipolysis, triglyceride-free fatty acid (FFA) cycling, FFA oxidation, and adipose tissue insulin sensitivity. Functional analysis of BAT and WAT demonstrated the greater thermogenic capacity of BAT compared to WAT, while molecular analysis revealed a cold-induced upregulation of genes involved in lipid metabolism only in BAT. The accelerated mobilization and oxidation of lipids upon BAT activation supports a putative role for BAT in the regulation of lipid metabolism in humans.