Biomarkers of Browning in Cold Exposed Siberian Adults

Cold-exposure promotes energy expenditure by inducing brown adipose tissue (BAT) thermogenesis, which over time, is also sustained by browning, the appearance, or increase, of brown-like cells into white fat depots. Identification of circulating markers reflecting BAT activity and browning is crucial to study this phenomenon and its triggers, also holding possible implications for the therapy of obesity and metabolic diseases. Using RT-qPCR, we evaluated the peripheral blood mononuclear cells (PBMC) expression profile of regulators of BAT activity (CIDEA, PRDM16), white adipocytes browning (HOXC9 and SLC27A1), and fatty acid β-oxidation (CPT1A) in 150 Siberian healthy miners living at extremely cold temperatures compared to 29 healthy subjects living in thermoneutral conditions. Anthropometric parameters, glucose, and lipid profiles were also assessed. The cold-exposed group showed significantly lower weight, BMI, hip circumference, and PBMC expression of CIDEA, but higher expression of HOXC9 and higher circulating glucose compared to controls. Within the cold-exposed group, BMI, total cholesterol, and the atherogenic coefficient were lower in individuals exposed to low temperatures for a longer time. In conclusion, human PBMC expresses the brown adipocytes marker CIDEA and the browning marker HOXC9, which, varying according to cold-exposure, possibly reflect changes in BAT activation and white fat browning.

[1]  E. Nisoli,et al.  COVID-19 and fat embolism: a hypothesis to explain the severe clinical outcome in people with obesity , 2020, International Journal of Obesity.

[2]  O. Dekkers,et al.  European Society of Endocrinology Clinical Practice Guideline: Endocrine work-up in obesity. , 2020, European journal of endocrinology.

[3]  M. Protasoni,et al.  A large proportion of mediastinal and perirenal visceral fat of Siberian adult people is formed by UCP1 immunoreactive multilocular and paucilocular adipocytes , 2019, Journal of Physiology and Biochemistry.

[4]  Gail M. Williams,et al.  The nonlinear association between outdoor temperature and cholesterol levels, with modifying effect of individual characteristics and behaviors , 2019, International Journal of Biometeorology.

[5]  Kyoung-Jae Won,et al.  A PRDM16-Driven Metabolic Signal from Adipocytes Regulates Precursor Cell Fate. , 2019, Cell metabolism.

[6]  S. Cinti.  Anatomy and physiology of the nutritional system. , 2019, Molecular aspects of medicine.

[7]  V. Puri,et al.  CIDE Proteins in Human Health and Disease , 2019, Cells.

[8]  D. Guertin,et al.  Brown Adipose Tissue Development and Metabolism. , 2019, Handbook of experimental pharmacology.

[9]  A. Pfeifer,et al.  MicroRNAs in brown and beige fat. , 2019, Biochimica et biophysica acta. Molecular and cell biology of lipids.

[10]  K. Kristiansen,et al.  Dietary Proteins, Brown Fat, and Adiposity , 2018, Front. Physiol..

[11]  E. Nisoli,et al.  Neuroendocrinology of Energy Balance , 2018 .

[12]  F. Villarroya,et al.  Brown adipose tissue as a secretory organ , 2017, Nature Reviews Endocrinology.

[13]  S. Kajimura,et al.  Transcriptional and epigenetic control of brown and beige adipose cell fate and function , 2016, Nature Reviews Molecular Cell Biology.

[14]  S. Kajimura,et al.  Transcriptional and epigenetic control of brown and beige adipose cell fate and function , 2016, Nature Reviews Molecular Cell Biology.

[15]  S. Cinti,et al.  Convertible visceral fat as a therapeutic target to curb obesity , 2016, Nature Reviews Drug Discovery.

[16]  C. Qualls,et al.  The FTO gene is associated with a paradoxically favorable cardiometabolic risk profile in frail, obese older adults , 2016, Pharmacogenetics and genomics.

[17]  Judith Klein-Seetharaman,et al.  The brown adipocyte protein CIDEA promotes lipid droplet fusion via a phosphatidic acid-binding amphipathic helix , 2015, eLife.

[18]  A. Palou,et al.  Gene expression of peripheral blood mononuclear cells is affected by cold exposure. , 2015, American journal of physiology. Regulatory, integrative and comparative physiology.

[19]  L. Sidossis,et al.  Genetic and functional characterization of clonally derived adult human brown adipocytes , 2015, Nature Medicine.

[20]  J. Esko,et al.  Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development , 2015, Nature Communications.

[21]  Clark R. Andersen,et al.  Brown Adipose Tissue Improves Whole-Body Glucose Homeostasis and Insulin Sensitivity in Humans , 2014, Diabetes.

[22]  P. Scherer,et al.  Tracking adipogenesis during white adipose tissue development, expansion and regeneration , 2013, Nature Medicine.

[23]  Mami Matsushita,et al.  Recruited brown adipose tissue as an antiobesity agent in humans. , 2013, The Journal of clinical investigation.

[24]  T. Rülicke,et al.  Bi-directional interconversion of brite and white adipocytes , 2013, Nature Cell Biology.

[25]  A. Carpentier,et al.  Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. , 2012, The Journal of clinical investigation.

[26]  J. Timmons,et al.  Recruited vs. nonrecruited molecular signatures of brown, "brite," and white adipose tissues. , 2012, American journal of physiology. Endocrinology and metabolism.

[27]  Oliver T. Bruns,et al.  Brown adipose tissue activity controls triglyceride clearance , 2011, Nature Medicine.

[28]  K. Kristiansen,et al.  The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. , 2010, American journal of physiology. Endocrinology and metabolism.

[29]  CJ ikewuch,et al.  Alteration of Plasma Lipid Profiles and Atherogenic Indices by Stachytarpheta jamaicensis L. (Vahl) , 2010 .

[30]  B. Cannon,et al.  The changed metabolic world with human brown adipose tissue: therapeutic visions. , 2010, Cell metabolism.

[31]  W. D. van Marken Lichtenbelt,et al.  Cold-activated brown adipose tissue in healthy men. , 2009, The New England journal of medicine.

[32]  Takahiro Shimizu,et al.  Acute cold exposure-induced down-regulation of CIDEA, cell death-inducing DNA fragmentation factor-alpha-like effector A, in rat interscapular brown adipose tissue by sympathetically activated beta3-adrenoreceptors. , 2009, Biochemical and biophysical research communications.

[33]  Jan Nedergaard,et al.  The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[34]  E. Palmer,et al.  Identification and importance of brown adipose tissue in adult humans. , 2009, The New England journal of medicine.

[35]  A. Chawla,et al.  Cidea is associated with lipid droplets and insulin sensitivity in humans , 2008, Proceedings of the National Academy of Sciences.

[36]  Jan Nedergaard,et al.  Brown adipose tissue: function and physiological significance. , 2004, Physiological reviews.

[37]  B. Lowell,et al.  βAR Signaling Required for Diet-Induced Thermogenesis and Obesity Resistance , 2002, Science.