Brown Adipose Tissue Exhibits a Glucose-Responsive Thermogenic Biorhythm in Humans

Paul Lee; Ron Bova; Lynne Schofield; Wendy Bryant; William Dieckmann; Anthony Slattery; Matt A Govendir; Louise Emmett; Jerry R Greenfield

doi:10.1016/j.cmet.2016.02.007

Brown Adipose Tissue Exhibits a Glucose-Responsive Thermogenic Biorhythm in Humans

Cell Metab. 2016 Apr 12;23(4):602-9. doi: 10.1016/j.cmet.2016.02.007. Epub 2016 Mar 10.

Authors

Paul Lee¹, Ron Bova², Lynne Schofield³, Wendy Bryant⁴, William Dieckmann⁵, Anthony Slattery⁶, Matt A Govendir⁷, Louise Emmett⁶, Jerry R Greenfield⁸

Affiliations

¹ Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; Department of Endocrinology, St. Vincent's Hospital, Sydney, NSW 2010, Australia; Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: p.lee@garvan.org.au.
² Department of Surgery, St. Vincent's Hospital, Sydney, NSW 2010, Australia.
³ Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; Department of Endocrinology, St. Vincent's Hospital, Sydney, NSW 2010, Australia.
⁴ Diabetes Centre, St. Vincent's Hospital, Sydney, NSW 2010, Australia.
⁵ Department of Positron Emission Tomography, National Institutes of Health, Bethesda, MD 20892, USA.
⁶ Department of PET and Nuclear Medicine, St. Vincent's Hospital, Sydney, NSW 2010, Australia.
⁷ Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
⁸ Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; Department of Endocrinology, St. Vincent's Hospital, Sydney, NSW 2010, Australia; Diabetes Centre, St. Vincent's Hospital, Sydney, NSW 2010, Australia; Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia.

PMID: 26972823
DOI: 10.1016/j.cmet.2016.02.007

Abstract

High abundance of brown adipose tissue (BAT) is linked to lower glycaemia in humans, leading to the belief that BAT may protect against diabetes. The relationship between BAT glucose utilization and systemic glucose homeostasis has not been defined. In this paper we have characterized glycaemic excursions and BAT thermogenic responses in human brown adipocytes, BAT explants, and healthy adults through supraclavicular temperature profiling, revealing their circadian coupling in vivo and in vitro, orchestrated by UCP1, GLUT4, and Rev-erbα biorhythms. Extent of glycated haemoglobin also correlated positively with environmental temperature among community-dwelling patients. These data uncover potential crosstalk between BAT and glucose regulatory pathways, evident on cellular, tissue, individual, and population levels, and provide impetus to search for BAT harnessing strategies for therapeutic purposes.

Keywords: GLUT4; Rev-erb; UCP1; beige adipose; circadian.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipocytes, Brown / metabolism
Adipose Tissue, Brown / physiology*
Adult
Cells, Cultured
Circadian Rhythm*
Female
Glucose / metabolism*
Glucose Transporter Type 4 / metabolism
Humans
Male
Middle Aged
Nuclear Receptor Subfamily 1, Group D, Member 1 / metabolism
Thermogenesis*
Uncoupling Protein 1 / metabolism
Young Adult

Substances

Glucose Transporter Type 4
NR1D1 protein, human
Nuclear Receptor Subfamily 1, Group D, Member 1
SLC2A4 protein, human
UCP1 protein, human
Uncoupling Protein 1
Glucose