Metabolic Improvement Via Enhancing Thermogenic Fat-Mediated Non-shivering Thermogenesis: From Rodents to Humans

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2020 Oct 5

PMID 33013706

Citations 9

Authors

Ruping Pan

Xiaohua Zhu

Pema Maretich

Yong Chen

Affiliations

Soon will be listed here.

Abstract

Brown and beige adipose tissues play a large role in non-shivering thermogenesis (NST) in mammals, and subsequently have been studied for decades as potential therapeutic targets to treat obesity and its related metabolic diseases. However, the mechanistic regulation of brown/beige adipose tissue induction and maintenance in humans is very limited due to the ethical reasons. In fact, metabolic signaling has primarily been investigated using rodent models. A better understanding of non-shivering thermogenesis in humans is thus vital and urgent in order to treat obesity by targeting human brown adipose tissue (BAT). In this review, we summarize the anatomical and physiological differences between rodent and human BAT, current useful and mostly non-invasive methods in studying human BAT, as well as recent advancements targeting thermogenic adipocytes as a means to combat metabolic diseases in humans. Furthermore, we also discuss several novel relevant strategies of therapeutic interventions, which has been attempted in rodent experiments, and possible future investigations in humans in this field.

Citing Articles

Hypoxia-inducible factor-1α-deficient adipose-tissue macrophages produce the heat to mediate lipolysis of white adipose tissue through uncoupling protein-1.

Kang G, Kim Y, Oh H, Jo H, Bok S, Jeon Y Lab Anim Res. 2024; 40(1):37.

PMID: 39473019 PMC: 11523771. DOI: 10.1186/s42826-024-00224-4.

Effects of N-acetylcysteine on the expressions of UCP1 and factors related to thyroid function in visceral adipose tissue of obese adults: a randomized, double-blind clinical trial.

Sohouli M, Eslamian G, Ardehali S, Raeissadat S, Shimi G, Pourvali K Genes Nutr. 2024; 19(1):8.

PMID: 38702594 PMC: 11069202. DOI: 10.1186/s12263-024-00744-7.

Brown Fat and Nutrition: Implications for Nutritional Interventions.

Noriega L, Yang C, Wang C Nutrients. 2023; 15(18).

PMID: 37764855 PMC: 10536824. DOI: 10.3390/nu15184072.

Loss of cAMP Signaling in CD11c Immune Cells Protects Against Diet-Induced Obesity.

Zeng L, Herdman D, Lee S, Tao A, Das M, Bertin S Diabetes. 2023; 72(9):1235-1250.

PMID: 37257047 PMC: 10451016. DOI: 10.2337/db22-1035.

The ABA/LANCL Hormone/Receptor System in the Control of Glycemia, of Cardiomyocyte Energy Metabolism, and in Neuroprotection: A New Ally in the Treatment of Diabetes Mellitus?.

Spinelli S, Magnone M, Guida L, Sturla L, Zocchi E Int J Mol Sci. 2023; 24(2).

PMID: 36674711 PMC: 9863406. DOI: 10.3390/ijms24021199.

References

Vonesh E, Gooch K, Khangulov V, Schermer C, Johnston K, Szabo S . Cardiovascular risk profile in individuals initiating treatment for overactive bladder - Challenges and learnings for comparative analysis using linked claims and electronic medical record databases. PLoS One. 2018; 13(10):e0205640. PMC: 6191128. DOI: 10.1371/journal.pone.0205640. View

Ouellet V, Labbe S, Blondin D, Phoenix S, Guerin B, Haman F . Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. J Clin Invest. 2012; 122(2):545-52. PMC: 3266793. DOI: 10.1172/JCI60433. View

Seale P, Conroe H, Estall J, Kajimura S, Frontini A, Ishibashi J . Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. J Clin Invest. 2010; 121(1):96-105. PMC: 3007155. DOI: 10.1172/JCI44271. View

Keam S . Vibegron: First Global Approval. Drugs. 2018; 78(17):1835-1839. DOI: 10.1007/s40265-018-1006-3. View

U Din M, Raiko J, Saari T, Kudomi N, Tolvanen T, Oikonen V . Human brown adipose tissue [(15)O]O2 PET imaging in the presence and absence of cold stimulus. Eur J Nucl Med Mol Imaging. 2016; 43(10):1878-86. PMC: 4969352. DOI: 10.1007/s00259-016-3364-y. View

Frontini A, Vitali A, Perugini J, Murano I, Romiti C, Ricquier D . White-to-brown transdifferentiation of omental adipocytes in patients affected by pheochromocytoma. Biochim Biophys Acta. 2013; 1831(5):950-9. DOI: 10.1016/j.bbalip.2013.02.005. View

Vishvanath L, MacPherson K, Hepler C, Wang Q, Shao M, Spurgin S . Pdgfrβ+ Mural Preadipocytes Contribute to Adipocyte Hyperplasia Induced by High-Fat-Diet Feeding and Prolonged Cold Exposure in Adult Mice. Cell Metab. 2015; 23(2):350-9. PMC: 4749445. DOI: 10.1016/j.cmet.2015.10.018. View

Zhang Z, Cheng H, Onishi K, Ohte N, Wannenburg T, Cheng C . Enhanced inhibition of L-type Ca2+ current by beta3-adrenergic stimulation in failing rat heart. J Pharmacol Exp Ther. 2005; 315(3):1203-11. DOI: 10.1124/jpet.105.089672. View

Kalinovich A, de Jong J, Cannon B, Nedergaard J . UCP1 in adipose tissues: two steps to full browning. Biochimie. 2017; 134:127-137. DOI: 10.1016/j.biochi.2017.01.007. View

10.

Kir S, Spiegelman B . CACHEXIA & BROWN FAT: A BURNING ISSUE IN CANCER. Trends Cancer. 2017; 2(9):461-463. PMC: 5407404. DOI: 10.1016/j.trecan.2016.07.005. View

11.

Bhadada S, Patel B, Mehta A, Goyal R . β(3) Receptors: Role in Cardiometabolic Disorders. Ther Adv Endocrinol Metab. 2012; 2(2):65-79. PMC: 3474626. DOI: 10.1177/2042018810390259. View

12.

Bostrom P, Wu J, Jedrychowski M, Korde A, Ye L, Lo J . A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012; 481(7382):463-8. PMC: 3522098. DOI: 10.1038/nature10777. View

13.

Bachman E, Dhillon H, Zhang C, Cinti S, Bianco A, Kobilka B . betaAR signaling required for diet-induced thermogenesis and obesity resistance. Science. 2002; 297(5582):843-5. DOI: 10.1126/science.1073160. View

14.

Soundarrajan M, Deng J, Kwasny M, Rubert N, Nelson P, El-Seoud D . Activated brown adipose tissue and its relationship to adiposity and metabolic markers: an exploratory study. Adipocyte. 2020; 9(1):87-95. PMC: 7039639. DOI: 10.1080/21623945.2020.1724740. View

15.

Lidell M, Betz M, Dahlqvist Leinhard O, Heglind M, Elander L, Slawik M . Evidence for two types of brown adipose tissue in humans. Nat Med. 2013; 19(5):631-4. DOI: 10.1038/nm.3017. View

16.

Blondin D, Labbe S, Tingelstad H, Noll C, Kunach M, Phoenix S . Increased brown adipose tissue oxidative capacity in cold-acclimated humans. J Clin Endocrinol Metab. 2014; 99(3):E438-46. PMC: 4213359. DOI: 10.1210/jc.2013-3901. View

17.

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

18.

Long J, Svensson K, Tsai L, Zeng X, Roh H, Kong X . A smooth muscle-like origin for beige adipocytes. Cell Metab. 2014; 19(5):810-20. PMC: 4052772. DOI: 10.1016/j.cmet.2014.03.025. View

19.

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

20.

Steiner G, Loveland M, SCHONBAUM E . Effect of denervation on brown adipose tissue metabolism. Am J Physiol. 1970; 218(2):566-70. DOI: 10.1152/ajplegacy.1970.218.2.566. View