Lack of TRPV1 aggravates obesity-associated hypertension through the disturbance of mitochondrial Ca2+ homeostasis in brown adipose tissue.

Abstract

The combination of obesity and hypertension is associated with high morbidity and mortality; however, the mechanism underlying obesity-induced hypertension remains unclear. In this study, we detected the possible effects of TRPV1, a previously identified antihypertensive calcium (Ca2+) channel in adipose tissue, on the occurrence of obesity and hypertension in mice lacking UCP1, a spontaneously genetically manipulated obesity model, by generating TRPV1 and UCP1 double knockout mice. In these mice, obesity and hypertension appeared earlier and were more severe than in mice with the knockout of UCP1 or TRPV1 alone. The knockout of TRPV1 in UCP1 knockout mice further reduced functional brown adipose tissue (BAT) generation; decreased resting oxygen consumption, heat production, and locomotor activities; and was accompanied by severe mitochondrial respiratory dysfunction in BAT. Mechanistically, TRPV1, UCP1, and LETM1 acted as a complex to maintain an appropriate mitochondrial Ca2+ level, and TRPV1 knockout caused a compensatory increase in mitochondrial Ca2+ uptake via LETM1 activation. However, the compensatory response was blocked in UCP1-/- mice, resulting in dramatically reduced mitochondrial Ca2+ uptake and higher production of ATP and oxidative stress. This study provides in vivo evidence for the critical role of BAT mitochondrial Ca2+ homeostasis in obesity-associated hypertension and indicates that the TRPV1/UCP1/LETM1 complex may be an alternative intervention target.

• Authors: Li Li, Liqun Ma, Zhidan Luo, Xiao Wei, Yu Zhao, Cui Zhou, Aidi Mou, Zongshi Lu, Mei You, Chengkang He, Huan Ma, Qing Zhou, Lijuan Wang, Tingbing Cao, Yucun Gu, Peng Gao, Zhiming Zhu
• Journal: Hypertension research : official journal of the Japanese Society of Hypertension (Hypertens Res) Vol. 45 Issue 5 Pg. 789-801 (05 2022) ISSN: 1348-4214 [Electronic] England
• PMID: 35043013 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• TRPV Cation Channels
• TRPV1 protein, mouse
• Calcium

Topics

• Adipose Tissue, Brown (metabolism)
• Animals
• Calcium (metabolism)
• Homeostasis
• Hypertension (etiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Obesity (complications)
• TRPV Cation Channels (genetics)