Impacts of cold exposure on energy metabolism

Miao Yan; Shanjie Wang; Shaohong Fang; Mingyan E; Bo Yu

doi:10.1515/fzm-2024-0007

Impacts of cold exposure on energy metabolism

doi: 10.1515/fzm-2024-0007

Miao Yan^{1, 2, #},
Shanjie Wang^{1, 2, #},
Shaohong Fang^{1, 2},
Mingyan E³,
Bo Yu^{1, 2
, ,}

1.
Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, Harbin 150001, China
2.
The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin 150001, China
3.
Department of Thoracic Radiotherapy, Harbin Medical University Cancer Hospital, Harbin 150081, China

Funds:

the National Natural Science Foundation of China 82170262

Heilongjiang Province Applied Technology Research and Development Plan GA20C009

The Natural Science Foundation of Heilongjiang Province TD2020H001

More Information

Corresponding author: Bo Yu, Email: yubodr@163.com

摘要

Abstract: Cold stimulation has been shown to regulate glucose, lipid, and amino acid metabolism, while also increasing heat production and energy expenditure in the body. Disordered energy metabolism is a key factor in the onset and progression of chronic metabolic conditiones such as diabetes, obesity, and cardiovascular disease. Recent research has unveiled the myriad pathways through which cold stimulation affects human energy metabolism. This article provides an overview of how cold stimulation affects energy metabolism across the three major metabolic pathways. Furthermore, it explores the implications and potential therapeutic applications of cold stimulation in the prevention and treatment of various metabolic diseases.
- cold stimulation /
- energy metabolism /
- glucose metabolism /
- lipid metabolism /
- amino acid metabolism /
- chronic metabolic diseases

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Figure 1. Cold exposure affects energy metabolism and participates in the occurrence and development of metabolic diseases

BCAA, branched chain amino acids; TRL, triglyceride-rich lipoproteins.

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参考文献(77)

[1]	Alahmad B, Khraishah H, Roye D, et al. Associations between extreme temperatures and cardiovascular cause-specific mortality: results from 27 countries. Circulation, 2023; 147(1): 35-46. doi: 10.1161/CIRCULATIONAHA.122.061832
[2]	Bosy-Westphal A, Hagele F A, Muller M J. What is the impact of energy expenditure on energy intake? Nutrients, 2021; 13(10): 3508 doi: 10.3390/nu13103508
[3]	Liu F, Xiao Y, Ji X L, et al. The cAMP-PKA pathway-mediated fat mobilization is required for cold tolerance in C. elegans. Sci Rep, 2017; 7(1): 638. doi: 10.1038/s41598-017-00630-w
[4]	Straat M E, Jurado-Fasoli L, Ying Z, et al. Cold exposure induces dynamic changes in circulating triacylglycerol species, which is dependent on intracellular lipolysis: a randomized cross-over trial. EBioMedicine, 2022; 86: 104349. doi: 10.1016/j.ebiom.2022.104349
[5]	Kovanicova Z, Kurdiova T, Balaz M, et al. Cold exposure distinctively modulates parathyroid and thyroid hormones in cold-acclimatized and non-acclimatized humans. Endocrinology, 2020; 161(7): bqaa051 doi: 10.1210/endocr/bqaa051
[6]	Chen R, Yin P, Wang L, et al. Association between ambient temperature and mortality risk and burden: time series study in 272 main Chinese cities. BMJ, 2018; 363: k4306. doi: 10.1136/bmj.k4306
[7]	Chen Y, Ji H, Guo J, et al. Non-targeted metabolomics analysis based on LC-MS to assess the effects of different cold exposure times on piglets. Front Physiol, 2022; 13: 853995. doi: 10.3389/fphys.2022.853995
[8]	Ruperez C, Blasco-Roset A, Kular D, et al. Autophagy is Involved in cardiac remodeling in response to environmental temperature change. Front Physiol, 2022; 13: 864427. doi: 10.3389/fphys.2022.864427
[9]	Hanssen M J, Hoeks J, Brans B, et al. Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus. Nat Med, 2015; 21(8): 863-865. doi: 10.1038/nm.3891
[10]	Hanssen M J, Wierts R, Hoeks J, et al. Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance. Diabetologia, 2015; 58(3): 586-595. doi: 10.1007/s00125-014-3465-8
[11]	Lahesmaa M, Oikonen V, Helin S, et al. Regulation of human brown adipose tissue by adenosineand A2A receptors - studies with [15O]H2O and [11C]TMSX PET/CT. Eur J Nucl Med Mol Imaging, 2019; 46(3): 743-750. doi: 10.1007/s00259-018-4120-2
[12]	Matsushita M, Nirengi S, Hibi M, et al. Diurnal variations of brown fat thermogenesis and fat oxidation in humans. Int J Obes (Lond), 2021; 45(11): 2499-2505. doi: 10.1038/s41366-021-00927-x
[13]	Lee W C, Guntur A R, Long F. Energy metabolism of the osteoblast: implications for osteoporosis. Endocr Rev, 2017; 38(3): 255-266. doi: 10.1210/er.2017-00064
[14]	Riis-Vestergaard M J, Laustsen C, Mariager C O, et al. Glucose metabolism in brown adipose tissue determined by deuterium metabolic imaging in rats. Int J Obes (Lond), 2020; 44(6): 1417-1427. doi: 10.1038/s41366-020-0533-7
[15]	Kim Y C, Guan K L. mTOR: a pharmacologic target for autophagy regulation. J Clin Invest. 2015; 125(1): 25-32. doi: 10.1172/JCI73939
[16]	Hua H, Kong Q, Zhang H, et al. Targeting mTOR for cancer therapy. J Hematol Oncol, 2019; 12(1): 71. doi: 10.1186/s13045-019-0754-1
[17]	Castro E, Vieira T S, Oliveira T E, et al. Adipocyte-specific mTORC2 deficiency impairs BAT and iWAT thermogenic capacity without affecting glucose uptake and energy expenditure in cold-acclimated mice. Am J Physiol Endocrinol Metab, 2021; 321(5): E592-E605. doi: 10.1152/ajpendo.00587.2020
[18]	Lewis G F, Brubaker P L. The discovery of insulin revisited: lessons for the modern era. J Clin Invest, 2021; 131(1): e142239. doi: 10.1172/JCI142239
[19]	Harrison V S, Khan M H, Chamberlain C E, et al. The noble and often nobel role played by insulin-focused research in modern medicine. Diabetes Care, 2022; 45(1): 23-27. doi: 10.2337/dci21-0012
[20]	Scheel A K, Espelage L, Chadt A. Many ways to rome: exercise, cold exposure and diet-do they all affect BAT activation and WAT browning in the same manner? Int J Mol Sci, 2022; 23(9): 4759. doi: 10.3390/ijms23094759
[21]	Markan K R, Boland L K, King-McAlpin A Q, et al. Adipose TBX1 regulates beta-adrenergic sensitivity in subcutaneous adipose tissue and thermogenic capacity in vivo. Mol Metab, 2020; 36: 100965. doi: 10.1016/j.molmet.2020.02.008
[22]	Monfort-Pires M, U-Din M, Nogueira G A, et al. Short dietary intervention with olive oil increases brown adipose tissue activity in lean but not overweight subjects. J Clin Endocrinol Metab, 2021; 106(2): 472-484. doi: 10.1210/clinem/dgaa824
[23]	Nascimento E B M, Hangelbroek R W J, Hooiveld G, et al. Comparative transcriptome analysis of human skeletal muscle in response to cold acclimation and exercise training in human volunteers. BMC Med Genomics, 2020; 13(1): 124. doi: 10.1186/s12920-020-00784-z
[24]	Huang S, Cao L, Cheng H, et al. The blooming intersection of subfatin and metabolic syndrome. Rev Cardiovasc Med, 2021; 22(3): 799-805. doi: 10.31083/j.rcm2203086
[25]	Du Q, Wu J, Fischer C, et al. Generation of mega brown adipose tissue in adults by controlling brown adipocyte differentiation in vivo. Proc Natl Acad Sci USA, 2022; 119(40): e2203307119. doi: 10.1073/pnas.2203307119
[26]	Sellers A J, Pallubinsky H, Rense P, et al. The effect of cold exposure with shivering on glucose tolerance in healthy men. J Appl Physiol, 2021; 130(1): 193-205. doi: 10.1152/japplphysiol.00642.2020
[27]	Bahler L, Verberne H J, Admiraal W M, et al. Differences in sympathetic nervous stimulation of brown adipose tissue between the young and old, and the lean and obese. J Nucl Med, 2016; 57(3): 372-377. doi: 10.2967/jnumed.115.165829
[28]	Merchan-Ramirez E, Sanchez-Delgado G, Arrizabalaga-Arriazu C, et al. Thyroid function is not associated with brown adipose tissue volume and 18F-fluorodeoxyglucose uptake in young euthyroid adults. Eur J Endocrino, 2021; 185(2): 209-218. doi: 10.1530/EJE-21-0192
[29]	Park H J, Jang H R, Park S Y, et al. The essential role of fructose-1, 6-bisphosphatase 2 enzyme in thermal homeostasis upon cold stress. Exp Mol Med, 2020; 52(3): 485-496. doi: 10.1038/s12276-020-0402-4
[30]	Remmerie A, Scott CL. Macrophages and lipid metabolism. Cell Immunol, 2018; 330: 27-42. doi: 10.1016/j.cellimm.2018.01.020
[31]	Li Z, Zhang H. Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression. Cell Mol Life Sci, 2016; 73(2): 377-392. doi: 10.1007/s00018-015-2070-4
[32]	Straat M E, Martinez-Tellez B, Sardjoe Mishre A, et al. Cold-induced thermogenesis shows a diurnal variation that unfolds differently in males and females. J Clin Endocrinol Metab, 2022; 107(6): 1626-1635. doi: 10.1210/clinem/dgac094
[33]	Von Bank H, Kirsh C, Simcox J. Aging adipose: depot location dictates age-associated expansion and dysfunction. Ageing Res Rev, 2021; 67: 101259. doi: 10.1016/j.arr.2021.101259
[34]	Pernes G, Morgan P K, Huynh K, et al. Characterization of the circulating and tissue-specific alterations to the lipidome in response to moderate and major cold stress in mice. Am J Physiol Regul Integr Comp Physiol, 2021; 320(2): R95-104. doi: 10.1152/ajpregu.00112.2020
[35]	Crandall J P, Fraum T J, Wahl R L. Brown adipose tissue: a protective mechanism against "preprediabetes"? J Nucl Med, 2022; 63(9): 1433-1440. doi: 10.2967/jnumed.121.263357
[36]	Cero C, Lea H J, Zhu K Y, et al. beta3-Adrenergic receptors regulate human brown/beige adipocyte lipolysis and thermogenesis. JCI Insight, 2021; 6(11): e139160. doi: 10.1172/jci.insight.139160
[37]	Chen CC, Kuo C H, Leu Y L, et al. Corylin reduces obesity and insulin resistance and promotes adipose tissue browning through SIRT-1 and beta3-AR activation. Pharmacol Res, 2021; 164: 105291. doi: 10.1016/j.phrs.2020.105291
[38]	Sorensen-Zender I, Bhayana S, Susnik N, et al. Zinc-alpha2-Glycoprotein exerts antifibrotic effects in kidney and heart. J Am Soc Nephrol, 2015; 26(11): 2659-2668. doi: 10.1681/ASN.2014050485
[39]	Ryden M, Agustsson T, Andersson J, et al. Adipose zinc-alpha2-glycoprotein is a catabolic marker in cancer and noncancerous states. J Intern Med, 2012; 271(4): 414-420. doi: 10.1111/j.1365-2796.2011.02441.x
[40]	Fan G, Li Y, Ma F, et al. Zinc-alpha2-glycoprotein promotes skeletal muscle lipid metabolism in cold-stressed mice. Endocr J, 2021; 68(1): 53-62. doi: 10.1507/endocrj.EJ20-0179
[41]	Bjertnaes L J, Naesheim T O, Reierth E, et al. Physiological changes in subjects exposed to accidental hypothermia: an update. Front Med (Lausanne), 2022; 9: 824395. doi: 10.3389/fmed.2022.824395
[42]	Hong A E, Ryu M S, Lim I K. Proper regulation of beta-adrenergic signal requires Btg2 gene for lipolysis and thermogenesis in response to starvation or cold acclimation in female mice. J Nutr Biochem, 2023; 111: 109160. doi: 10.1016/j.jnutbio.2022.109160
[43]	Bleher M, Meshko B, Cacciapuoti I, et al. Egr1 loss-of-function promotes beige adipocyte differentiation and activation specifically in inguinal subcutaneous white adipose tissue. Sci Rep, 2020; 10(1): 15842. doi: 10.1038/s41598-020-72698-w
[44]	Miao Y, Qin H, Zhong Y, et al. Novel adipokine asprosin modulates browning and adipogenesis in white adipose tissue. J Endocrinol, 2021; 249(2): 83-93. doi: 10.1530/JOE-20-0503
[45]	Romere C, Duerrschmid C, Bournat J, et al. Asprosin, a fasting-induced glucogenic protein hormone. Cell, 2016; 165(3): 566-579. doi: 10.1016/j.cell.2016.02.063
[46]	Shamsi F, Wang C H, Tseng Y H. The evolving view of thermogenic adipocytes - ontogeny, niche and function. Nat Rev Endocrinol, 2021; 17(12): 726-744. doi: 10.1038/s41574-021-00562-6
[47]	Shamsi F, Xue R, Huang T L, et al. FGF6 and FGF9 regulate UCP1 expression independent of brown adipogenesis. Nat Commun, 2020; 11(1): 1421. doi: 10.1038/s41467-020-15055-9
[48]	Tabe Y, Lorenzi P L, Konopleva M. Amino acid metabolism in hematologic malignancies and the era of targeted therapy. Blood, 2019; 134(13): 1014-1023. doi: 10.1182/blood.2019001034
[49]	Li C, Wu B, Li Y, et al. Amino acid catabolism regulates hematopoietic stem cell proteostasis via a GCN2-eIF2alpha axis. Cell Stem Cell, 2022; 29(7): 1119-1134 doi: 10.1016/j.stem.2022.06.004
[50]	Yang L, Chu Z, Liu M, et al. Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy. J Hematol Oncol, 2023; 16(1): 59. doi: 10.1186/s13045-023-01453-1
[51]	McGarrah R W, White P J. Branched-chain amino acids in cardiovascular disease. Nat Rev Cardiol, 2023; 20(2): 77-89. doi: 10.1038/s41569-022-00760-3
[52]	Huang Y, Zhou M, Sun H, et al. Branched-chain amino acid metabolism in heart disease: an epiphenomenon or a real culprit? Cardiovasc Res, 2011; 90(2): 220-223. doi: 10.1093/cvr/cvr070
[53]	Li Y, Ping X, Zhang Y, et al. Comparative transcriptome profiling of cold exposure and beta3-AR agonist CL316, 243-induced browning of white fat. Front Physiol, 2021; 12: 667-698. doi: 10.3389/fphys.2021.667698
[54]	Teng T, Song X, Sun G, et al. Glucose supplementation improves intestinal amino acid transport and muscle amino acid pool in pigs during chronic cold exposure. Anim Nutr, 2023; 12: 360-374. doi: 10.1016/j.aninu.2022.10.009
[55]	Yoneshiro T, Wang Q, Tajima K, et al. BCAA catabolism in brown fat controls energy homeostasis through SLC25A44. Nature, 2019; 572(7771): 614-619. doi: 10.1038/s41586-019-1503-x
[56]	Cannavino J, Shao M, An YA, et al. Regulation of cold-induced thermogenesis by the RNA binding protein FAM195A. Proc Natl Acad Sci USA, 2021; 118(23): e2104650118. doi: 10.1073/pnas.2104650118
[57]	Cruzat V, Macedo Rogero M, Noel Keane K, et al. Glutamine: metabolism and immune function, supplementation and clinical translation. Nutrients, 2018; 10(11): 1564 doi: 10.3390/nu10111564
[58]	Smedberg M, Wernerman J. Is the glutamine story over? Crit Care, 2016; 20(1): 361. doi: 10.1186/s13054-016-1531-y
[59]	Okamatsu-Ogura Y, Kuroda M, Tsutsumi R, et al. UCP1-dependent and UCP1-independent metabolic changes induced by acute cold exposure in brown adipose tissue of mice. Metabolism, 2020; 113: 154396. doi: 10.1016/j.metabol.2020.154396
[60]	Lian S, Li W, Wang D, et al. Effects of prenatal cold stress on maternal serum metabolomics in rats. Life Sci, 2020; 246: 117432. doi: 10.1016/j.lfs.2020.117432
[61]	Shahcheraghi S H, Aljabali A A A, Al Zoubi M S, et al. Overview of key molecular and pharmacological targets for diabetes and associated diseases. Life Sci, 2021; 278: 119632. doi: 10.1016/j.lfs.2021.119632
[62]	Aubert G, Vega R B, Kelly D P. Perturbations in the gene regulatory pathways controlling mitochondrial energy production in the failing heart. Biochim Biophys Acta, 2013; 1833(4): 840-847. doi: 10.1016/j.bbamcr.2012.08.015
[63]	Samuel V T, Petersen K F, Shulman G I. Lipid-induced insulin resistance: unravelling the mechanism. Lancet, 2010; 375(9733): 2267-2277. doi: 10.1016/S0140-6736(10)60408-4
[64]	Remie C M E, Moonen M P B, Roumans K H M, et al. Metabolic responses to mild cold acclimation in type 2 diabetes patients. Nat Commun, 2021; 12(1): 1516. doi: 10.1038/s41467-021-21813-0
[65]	Pace N P, Vassallo J, Calleja-Agius J. Gestational diabetes, environmental temperature and climate factors - from epidemiological evidence to physiological mechanisms. Early Hum Dev, 2021; 155: 105219. doi: 10.1016/j.earlhumdev.2020.105219
[66]	Perez L C, Perez L T, Nene Y, et al. Interventions associated with brown adipose tissue activation and the impact on energy expenditure and weight loss: a systematic review. Front Endocrinol (Lausanne), 2022; 13: 1037458. doi: 10.3389/fendo.2022.1037458
[67]	Um J H, Park S Y, Hur J H, et al. Bone morphogenic protein 9 is a novel thermogenic hepatokine secreted in response to cold exposure. Metabolism, 2022; 129: 155139. doi: 10.1016/j.metabol.2022.155139
[68]	Aldiss P, Lewis J E, Lupini I, et al. Cold exposure drives weight gain and adiposity following chronic suppression of brown adipose tissue. Int J Mol Sci, 2022; 23(3): 1869 doi: 10.3390/ijms23031869
[69]	Yuneva M. Cold exposure as anti-cancer therapy. Cancer Cell, 2022; 40(10): 1092-1094. doi: 10.1016/j.ccell.2022.09.008
[70]	Tseng Y H. Adipose tissue in communication: within and without. Nat Rev Endocrinol, 2023; 19(2): 70-71. doi: 10.1038/s41574-022-00789-x
[71]	Seki T, Yang Y, Sun X, et al. Brown-fat-mediated tumour suppression by cold-altered global metabolism. Nature, 2022; 608(7922): 421-428. doi: 10.1038/s41586-022-05030-3
[72]	Gandhi S, Oshi M, Murthy V, et al. Enhanced thermogenesis in triple-negative breast cancer is associated with pro-tumor immune microenvironment. Cancers (Basel), 2021; 13(11): 2559. doi: 10.3390/cancers13112559
[73]	Schaltenberg N, John C, Heine M, et al. Endothelial lipase is involved in cold-induced high-density lipoprotein turnover and reverse cholesterol transport in Mice. Front Cardiovasc Med, 2021; 8: 628235. doi: 10.3389/fcvm.2021.628235
[74]	Ying Z, van Eenige R, Beerepoot R, et al. Mirabegron-induced brown fat activation does not exacerbate atherosclerosis in mice with a functional hepatic ApoE-LDLR pathway. Pharmacol Res, 2023; 187: 106634. doi: 10.1016/j.phrs.2022.106634
[75]	Kong X, Liu H, He X, et al. Unraveling the mystery of cold stress-induced myocardial injury. Front Physiol, 2020; 11: 580811. doi: 10.3389/fphys.2020.580811
[76]	Kashiwagi Y, Komukai K, Kimura H, et al. Therapeutic hypothermia after cardiac arrest increases the plasma level of B-type natriuretic peptide. Sci Rep, 2020; 10(1): 15545. doi: 10.1038/s41598-020-72703-2
[77]	Wu C I, Lu Y Y, Chen Y C, et al. The AMP-activated protein kinase modulates hypothermia-induced J wave. Eur J Clin Invest, 2020; 50(6): e13247. doi: 10.1111/eci.13247