Abstract

Beige fat is a potential therapeutic target for obesity and other metabolic diseases due to its inducible brown fat-like functions. Inguinal white adipose tissue (iWAT) can undergo robust brown remodeling with appropriate stimuli and is therefore widely considered as a representative beige fat depot. However, adipose tissues residing in different anatomic depots exhibit a broad range of plasticity, raising the possibility that better beige fat depots with greater plasticity may exist. Here we identified and characterized a novel, naturally-existing beige fat depot, thigh adipose tissue (tAT). Unlike classic WATs, tAT maintains beige fat morphology at room temperature, whereas high-fat diet (HFD) feeding or aging promotes the development of typical WAT features, namely unilocular adipocytes. The brown adipocyte gene expression in tAT is consistently higher than in iWAT under cold exposure, HFD feeding, and rosiglitazone treatment conditions. Our molecular profiling by RNA-Seq revealed up-regulation of energy expenditure pathways and repressed inflammation in tAT relative to eWAT and iWAT. Furthermore, we demonstrated that the master fatty acid oxidation regulator peroxisome proliferator-activated receptor α is dispensable for maintaining and activating the beige character of tAT. Therefore, we have identified tAT as a natural beige adipose depot in mice with a unique molecular profile that does not require peroxisome proliferator-activated receptor α.

Highlights

  • Beige fat is a potential therapeutic target for obesity and other metabolic diseases due to its inducible brown fat-like functions

  • We first noticed a small fat pad located toward the dorsal end of inguinal fat that was darker in color (Fig. 1A, top panel). This depot does not belong to any of the three divisions of Inguinal white adipose tissue (iWAT) [25, 26]; it attaches to the thigh, and we named it thigh adipose tissue

  • The current study indicates that thigh adipose tissue (tAT) is hyperplastic and has a dramatic browning potential, as observed through its significantly higher expression of brown fat markers than iWAT

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Summary

ARTICLE cro Identification of a natural beige adipose depot in mice

Thermogenic adipocytes in the form of BAT has been discovered in multiple locations, including the axillary, cervical, supraclavicular, paravertebral, and abdominal subcutaneous regions [17] Transcriptional analyses of these adipose depots, indicate that most human BAT expresses molecular markers selective to beige adipocytes in mice and do not express canonical. Numerous adipose depots exist in a variety of anatomic locations and exhibit a broad range of metabolic activity [24] This engenders the possibility that other fat depots may have higher browning capacities than iWAT and may serve as alternative or even superior beige fat sources. We identified an adipose depot in mice, adjacent to iWAT and attached to the thigh, which possesses higher browning potential than iWAT and expresses BAT-selective markers even without environmental stimuli; this fat depot may serve as a more appropriate model for brown remodeling studies

Results
Global transcriptome revealed tAT as a distinct fat depot
Discussion
Animal studies
RNA analysis
Statistical analysis
Full Text
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