Abstract
The recruitment of brite (or beige) adipocytes has been advocated as a means to combat obesity, due to their ability to phenotypically resemble brown adipocytes (BA). Lineage studies indicate that brite adipocytes are formed by differentiation of precursor cells or by direct conversion of existing white adipocytes, depending on the adipose depot examined. We have systematically compared the gene expression profile and a functional output (oxygen consumption) in mouse adipocytes cultured from two contrasting depots, namely interscapular brown adipose tissue, and inguinal white adipose tissue (iWAT), following treatment with a known browning agent, the peroxisome proliferator-activated receptor (PPARγ) activator rosiglitazone. Prototypical BA readily express uncoupling protein (UCP)1, and upstream regulators including the β3-adrenoceptor and transcription factors involved in energy homeostasis. Adipocytes from inguinal WAT display maximal UCP1 expression and mitochondrial uncoupling only when treated with a combination of the PPARγ activator rosiglitazone and a β3-adrenoceptor agonist. In conclusion, brite adipocytes are fully activated only when a browning agent (rosiglitazone) and a thermogenic agent (β3-adrenoceptor agonist) are added in combination. The presence of rosiglitazone throughout the 7-day culture period partially masks the effects of β3-adrenoceptor signaling in inguinal white adipocyte cultures, whereas including rosiglitazone only for the first 3 days promotes robust β3-adrenoceptor expression and provides an improved window for detection of β3-adrenoceptor responses.
Highlights
The remarkable prevalence of obesity worldwide has sparked considerable interest in therapeutic strategies that are effective and safe in promoting weight loss
From our overall profiling of gene expression using the custom qPCR array, we examined predicted upstream regulators (IPA) based on genes differentially expressed following 7d rosiglitazone in cultured adipocytes, and these regulators were compared to those predicted in brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) of mice subject to cold exposure for 2 days [26]
While there is a wealth of data on the gene expression of brite adipocytes [8, 9, 56, 62,63,64,65,66], these studies have generally aimed to identify differential genetic markers between brown, white, and brite adipocytes
Summary
The remarkable prevalence of obesity worldwide has sparked considerable interest in therapeutic strategies that are effective and safe in promoting weight loss. There are two types of adipose tissue with distinct functions: white adipose tissue (WAT) that stores chemical energy in the form of triacylglycerol, and brown adipose tissue (BAT) that releases chemical energy in the form of heat (thermogenesis). Classical BAT depots have been studied extensively in adult rodents. They are highly innervated and are activated by centers in the brain responsive to cold exposure, leading to the release of norepinephrine (NE) from sympathetic nerves. Upon binding of NE to BAT β3-adrenoceptors (β3-ARs), increased levels of intracellular cyclic AMP (cAMP) promote lipolysis, and this breakdown of triglycerides leads to release of free fatty acids that upregulate and activate uncoupling protein 1 (UCP1). Activated UCP1 uncouples mitochondrial respiration leading to heat generation, β3-AR signaling increases respiration and nonshivering thermogenesis, with prototypical BAT adipocytes being remarkably rich in mitochondria [1]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
