Adaptive Induction of Nonshivering Thermogenesis in Muscle Rather Than Brown Fat Could Counteract Obesity

Overview

Journal Physiol Res

Specialty Physiology

Date 2024 May 16

PMID 38752772

Authors

K Bardova

P Janovska

A Vavrova

J Kopecky

P Zouhar

Affiliations

Soon will be listed here.

Abstract

Warm-blooded animals such as birds and mammals are able to protect stable body temperature due to various thermogenic mechanisms. These processes can be facultative (occurring only under specific conditions, such as acute cold) and adaptive (adjusting their capacity according to long-term needs). They can represent a substantial part of overall energy expenditure and, therefore, affect energy balance. Classical mechanisms of facultative thermogenesis include shivering of skeletal muscles and (in mammals) non-shivering thermogenesis (NST) in brown adipose tissue (BAT), which depends on uncoupling protein 1 (UCP1). Existence of several alternative thermogenic mechanisms has been suggested. However, their relative contribution to overall heat production and the extent to which they are adaptive and facultative still needs to be better defined. Here we focus on comparison of NST in BAT with thermogenesis in skeletal muscles, including shivering and NST. We present indications that muscle NST may be adaptive but not facultative, unlike UCP1-dependent NST. Due to its slow regulation and low energy efficiency, reflecting in part the anatomical location, induction of muscle NST may counteract development of obesity more effectively than UCP1-dependent thermogenesis in BAT.

Citing Articles

Determination of the MEC90 of Oxycodone for Preventing Perioperative Shivering in Pregnant Patients Undergoing Caesarean Delivery with Neuraxial Anaesthesia: A Biased-Coin up-and-Down Sequential Allocation Trial.

Lu X, Chen K, Xuan Y, Shen M, Lei W, Huang Y Drug Des Devel Ther. 2025; 19:945-954.

PMID: 39959118 PMC: 11829597. DOI: 10.2147/DDDT.S497239.

Hyperactive browning and hypermetabolism: potentially dangerous element in critical illness.

Huang L, Zhu L, Zhao Z, Jiang S Front Endocrinol (Lausanne). 2024; 15():1484524.

PMID: 39640882 PMC: 11617193. DOI: 10.3389/fendo.2024.1484524.

References

Chen Y, Ikeda K, Yoneshiro T, Scaramozza A, Tajima K, Wang Q . Thermal stress induces glycolytic beige fat formation via a myogenic state. Nature. 2018; 565(7738):180-185. PMC: 6328316. DOI: 10.1038/s41586-018-0801-z. View

Bal N, Maurya S, Sopariwala D, Sahoo S, Gupta S, Shaikh S . Sarcolipin is a newly identified regulator of muscle-based thermogenesis in mammals. Nat Med. 2012; 18(10):1575-9. PMC: 3676351. DOI: 10.1038/nm.2897. View

Guerra C, Koza R, Yamashita H, Walsh K, Kozak L . Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity. J Clin Invest. 1998; 102(2):412-20. PMC: 508900. DOI: 10.1172/JCI3155. View

Bal N, Periasamy M . Uncoupling of sarcoendoplasmic reticulum calcium ATPase pump activity by sarcolipin as the basis for muscle non-shivering thermogenesis. Philos Trans R Soc Lond B Biol Sci. 2020; 375(1793):20190135. PMC: 7017432. DOI: 10.1098/rstb.2019.0135. View

Kazak L, Rahbani J, Samborska B, Lu G, Jedrychowski M, Lajoie M . Ablation of adipocyte creatine transport impairs thermogenesis and causes diet-induced obesity. Nat Metab. 2019; 1(3):360-370. PMC: 6544051. DOI: 10.1038/s42255-019-0035-x. View

Goldsmith R, Joanisse D, Gallagher D, Pavlovich K, Shamoon E, Leibel R . Effects of experimental weight perturbation on skeletal muscle work efficiency, fuel utilization, and biochemistry in human subjects. Am J Physiol Regul Integr Comp Physiol. 2009; 298(1):R79-88. PMC: 2806213. DOI: 10.1152/ajpregu.00053.2009. View

Oeckl J, Janovska P, Adamcova K, Bardova K, Brunner S, Dieckmann S . Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat. Mol Metab. 2022; 61:101499. PMC: 9097615. DOI: 10.1016/j.molmet.2022.101499. View

Flachs P, Adamcova K, Zouhar P, Marques C, Janovska P, Viegas I . Induction of lipogenesis in white fat during cold exposure in mice: link to lean phenotype. Int J Obes (Lond). 2016; 41(3):372-380. DOI: 10.1038/ijo.2016.228. View

Bombardier E, Smith I, Gamu D, Fajardo V, Vigna C, Sayer R . Sarcolipin trumps β-adrenergic receptor signaling as the favored mechanism for muscle-based diet-induced thermogenesis. FASEB J. 2013; 27(9):3871-8. PMC: 3752531. DOI: 10.1096/fj.13-230631. View

10.

Finlin B, Memetimin H, Confides A, Kasza I, Zhu B, Vekaria H . Human adipose beiging in response to cold and mirabegron. JCI Insight. 2018; 3(15). PMC: 6129119. DOI: 10.1172/jci.insight.121510. View

11.

Babu G, Bhupathy P, Timofeyev V, Petrashevskaya N, Reiser P, Chiamvimonvat N . Ablation of sarcolipin enhances sarcoplasmic reticulum calcium transport and atrial contractility. Proc Natl Acad Sci U S A. 2007; 104(45):17867-72. PMC: 2077025. DOI: 10.1073/pnas.0707722104. View

12.

Islam M, Sundaraj K, Ahmad R, Ahamed N . Mechanomyogram for muscle function assessment: a review. PLoS One. 2013; 8(3):e58902. PMC: 3594217. DOI: 10.1371/journal.pone.0058902. View

13.

Girardier L . The regulation of the biological furnace of warm blooded animals. Introduction. Experientia. 1977; 33(9):1121-2. DOI: 10.1007/BF01922276. View

14.

Kozak L . Brown fat and the myth of diet-induced thermogenesis. Cell Metab. 2010; 11(4):263-7. PMC: 2867325. DOI: 10.1016/j.cmet.2010.03.009. View

15.

Solinas G, Summermatter S, Mainieri D, Gubler M, Pirola L, Wymann M . The direct effect of leptin on skeletal muscle thermogenesis is mediated by substrate cycling between de novo lipogenesis and lipid oxidation. FEBS Lett. 2004; 577(3):539-44. DOI: 10.1016/j.febslet.2004.10.066. View

16.

Lowell B, Hamann A, Lawitts J, Himms-Hagen J, Boyer B, Kozak L . Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature. 1993; 366(6457):740-2. DOI: 10.1038/366740a0. View

17.

Feldmann H, Golozoubova V, Cannon B, Nedergaard J . UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab. 2009; 9(2):203-9. DOI: 10.1016/j.cmet.2008.12.014. View

18.

Kozak U, Kopecky J, Teisinger J, Enerback S, Boyer B, Kozak L . An upstream enhancer regulating brown-fat-specific expression of the mitochondrial uncoupling protein gene. Mol Cell Biol. 1994; 14(1):59-67. PMC: 358356. DOI: 10.1128/mcb.14.1.59-67.1994. View

19.

Nedergaard J, von Essen G, Cannon B . Brown adipose tissue: can it keep us slim? A discussion of the evidence for and against the existence of diet-induced thermogenesis in mice and men. Philos Trans R Soc Lond B Biol Sci. 2023; 378(1888):20220220. PMC: 10475870. DOI: 10.1098/rstb.2022.0220. View

20.

Ikeda K, Kang Q, Yoneshiro T, Camporez J, Maki H, Homma M . UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis. Nat Med. 2017; 23(12):1454-1465. PMC: 5727902. DOI: 10.1038/nm.4429. View