Tbx15 Defines a Glycolytic Subpopulation and White Adipocyte Heterogeneity

• Published in: Diabetes (New York, N.Y.) Vol. 66; no. 11; pp. 2822 - 2829
• Main Authors: Lee, Kevin Y, Sharma, Rita, Gase, Grant, Ussar, Siegfried, Li, Yichao, Welch, Lonnie, Berryman, Darlene E, Kispert, Andreas, Bluher, Matthias, Kahn, C Ronald
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01-11-2017
• Subjects: Adipocytes; Adipocytes, White - physiology; Adipose tissue; Animals; Body Weight; Cell Line; Female; Gene expression; Gene Expression Regulation - physiology; Genes; Glucose; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) - genetics; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) - metabolism; Glycolysis; Glycolysis - physiology; Hexokinase - genetics; Hexokinase - metabolism; Humans; Male; Metabolism; Mice; Mice, Inbred C57BL; Mutation; Obesity Studies; Oxidative metabolism; Preadipocytes; Skeletal muscle; Subcutaneous Fat - cytology; T-Box Domain Proteins - genetics; T-Box Domain Proteins - metabolism; T-box gene
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db17-0218

is a member of the T-box gene family of mesodermal developmental genes. We have recently shown that Tbx15 plays a critical role in the formation and metabolic programming of glycolytic myofibers in skeletal muscle.
is also differentially expressed among white adipose tissue (WAT) in different body depots. In the current study, using three independent methods, we show that even within a single WAT depot, high
expression is restricted to a subset of preadipocytes and mature white adipocytes. Gene expression and metabolic profiling demonstrate that the Tbx15
preadipocyte and adipocyte subpopulations of cells are highly glycolytic, whereas Tbx15
preadipocytes and adipocytes in the same depot are more oxidative and less glycolytic. Likewise, in humans, expression of
in subcutaneous and visceral WAT is positively correlated with markers of glycolytic metabolism and inversely correlated with obesity. Furthermore, overexpression of Tbx15 is sufficient to reduce oxidative and increase glycolytic metabolism in cultured adipocytes. Thus, Tbx15 differentially regulates oxidative and glycolytic metabolism within subpopulations of white adipocytes and preadipocytes. This leads to a functional heterogeneity of cellular metabolism within WAT that has potential impact in the understanding of human metabolic diseases.