Abstract
Beige adipocytes are newly identified thermogenic-poised adipocytes that could be activated by cold or β3-adrenergic receptor (β3-AR) signaling and offer therapeutic potential for treating obesity and metabolic diseases. Here we applied RNA-sequencing analysis in the beige fat of mice under cold exposure or β3-AR agonist CL316,243 (CL) treatment to provide a comparative and comprehensive analysis for the similarity and heterogeneity of these two stimulants. Importantly, via KEGG analysis, we found that cold and CL commonly induced oxidative phosphorylation. Meanwhile, cold increased glycerolipid and amino acids metabolism while CL treatment triggered a broader spectrum of metabolic responses including carbohydrate metabolism. Besides, cold or CL treatment featured greater heterogeneity in downregulated gene programs. Of note, the top changed genes in each category were confirmed by qPCR analysis. Overall, our analysis provided a better understanding of the heterogeneity of differential models for beige adipocytes activation and a possible clue for optimizing β3-AR agonists in the future.
Highlights
Obesity, manifested as excess fat accumulation caused by the imbalance between energy intake and expenditure, is a severe public health crisis throughout the world since it is the major risk factor for metabolic diseases including type 2 diabetes, hypertension, cardiovascular disease, and certain types of cancers (Harms and Seale, 2013)
To confirm the effects of cold exposure or β3-adrenergic receptor (β3-AR) agonist stimulation on the browning of white fat, two groups of mice at 8 weeks old were kept under either room temperature (RT, 22◦C) or 4◦C for 7 days, while the other two groups of mice of a similar age were intraperitoneally (IP) administrated with PBS or CL316,243 (CL) at RT for 7 days (Figure 1A)
Cold exposure exhibited strong effects on increasing food intake compared to CL treatment, which was consistent with previous reports (Yoshida et al, 1996; Jia et al, 2016; Xu et al, 2019)
Summary
Obesity, manifested as excess fat accumulation caused by the imbalance between energy intake and expenditure, is a severe public health crisis throughout the world since it is the major risk factor for metabolic diseases including type 2 diabetes, hypertension, cardiovascular disease, and certain types of cancers (Harms and Seale, 2013). Beige adipocytes have been discovered and characterized by their high thermogenic and energy dissipating capacity upon cold exposure or β3-adrenergic signaling (Himms-Hagen et al, 1994; Rosell et al, 2014), which is called the “browning of white fat.”. The browning phenomenon was observed in cold-exposed human adults in the supraclavicular region revealed by PET-CT scans with characteristics resembling beige/brown adipocytes in rodents (Nedergaard et al, 2007; Sharp et al, 2012). The existence of beige/brown fat in human adults has attracted great attention and has been considered a novel peripheral target to treat obesity and metabolic diseases
Sign-in/Register to view highlights & summary 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.
