title: Cold exposure stimulates lipid metabolism, induces inflammatory response in the adipose tissue of mice and promotes the osteogenic differentiation of BMMSCs via the p38 MAPK pathway in vitro.
abstract: This study was to explore the effect of long-term cold exposure on morphological changes of WAT and BAT, metabolic changes and inflammatory responses in vivo. We also investigated the effect of cold exposure on the osteogenic differentiation of BMMSCs and the mechanism involved in vitro. At the end of the animal experiments, WAT and BAT were isolated and analyzed by HE staining. The results showed that both temperature and exposure time were associated with the degree of WAT browning. Then, peripheral blood samples were collected and centrifuged to obtain serum. Serum biochemical analysis was performed. After exposure to cold air for 21 d, cyclic adenosine monophosphate (cAMP) level in BAT was greatly upregulated. cAMP in WAT and glycerol levels were slightly increased. Cold exposure decreased triglyceride (TG) level and increased the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). Whereas, high-density lipoprotein cholesterol (HDL-C) and free fatty acid (FFA) levels remains unchanged. Moreover, leptin and adiponectin (ADP) levels were remarkably downregulated. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 concentrations were significantly elevated. Furthermore, the results showed that cold exposure significantly elevated runt-related transcription factor 2 (Runx2), bone sialoprotein (BSP), osteopontin (OPN) and collagen I levels and promoted the phosphorylation of p38 MAPK. However, the inducing effects were greatly inhibited by p38 MAPK inhibitor SB203580. These data suggest that long-term cold exposure activate BAT, increase lipolysis rate and enhance inflammatory response in mice. Furthermore, cold exposure promoted the osteogenic differentiation of BMMSCs partially via the p38 MAPK pathway.
authors.affiliation: Physical Examination Center, The Second Affiliated Hospital of Harbin Medical University Harbin 150001, People's Republic of China.
authors.forename: Yizhen
authors.initials: Y
authors.lastname: Nie
authors.affiliation: Physical Examination Center, The Second Affiliated Hospital of Harbin Medical University Harbin 150001, People's Republic of China.
authors.forename: Zhaoqi
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Physical Examination Center, The Second Affiliated Hospital of Harbin Medical University Harbin 150001, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Medical Imaging, Harbin Fourth Hospital Harbin 150026, People's Republic of China.
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Cadre Ward, The Second Affiliated Hospital of Harbin Medical University Harbin 150001, People's Republic of China.
authors.forename: Yina
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D052436:Adipose Tissue, White / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003080:Cold Temperature; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000097:blood*; D004789:Enzyme Activation; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005990:Glycerol / Q000378:metabolism; D018836:Inflammation Mediators / Q000097:blood*; D008055:Lipids / Q000097:blood*; D008066:Lipolysis; D059630:Mesenchymal Stem Cells / Q000201:enzymology*; D008810:Mice, Inbred C57BL; D010012:Osteogenesis / Q000187:drug effects; D010641:Phenotype; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D016207:Cytokines; D005230:Fatty Acids, Nonesterified; D018836:Inflammation Mediators; D008055:Lipids; D047428:Protein Kinase Inhibitors; D014280:Triglycerides; D000242:Cyclic AMP; D048051:p38 Mitogen-Activated Protein Kinases; D005990:Glycerol
keywords: Adipose tissue; BMMSCs; WAT browning; cold exposure; lipolysis; osteogenic differentiation; p38 MAPK signalling pathway