Li Li, Baoguo Li, Min Li, John R. Speakman

Molecular Aspects of Medicine


Abstract
Endothermy requires a source of endogenous heat production. In birds, this is derived primarily from shivering, but in mammals it is mostly non-shivering thermogenesis (NST). Brown adipose tissue (BAT) is a specialized tissue found in Eutherian mammals that is the source of most NST. Heat production in BAT depends primarily on the activity of uncoupling protein 1 (UCP1), which decouples transport of protons across the inner mitochondrial membrane from synthesis of ATP. UCP1 and hence heat production of BAT is regulated by many factors. In this paper we discuss the main factors activating UCP1 and increasing heat production. Probably the most well-known activator is the catecholamine norepinephrine (NE) which is released from sympathetic nerve endings and binds to adrenergic receptors that are abundantly expressed on BAT. NE stimulates release of free-fatty acids. It was previously thought that such FFAs were essential for activation of UCP1. However recent work has suggested intracellular lipolysis is not essential and FFAs can be derived from extracellular sources. Thyroid hormones also exert impacts on metabolic rate via effects on brown adipocytes which express type 2 deiodinase. Knocking out DIO2 makes mice cold intolerant. Parathyroid hormone appears to also be a potent regulator of BAT activity and may be an important mediator of elevated expenditure during cancer cachexia, although this is disputed by observations that cachexia wasting is not blunted in UCP1 KO mice. Cardiac natriuretic peptides have also been implicated in regulating BAT thermogenesis and the interconversion of beige adipocytes from their white to brown form. Activation of BAT thermogenesis may be an important component of the post-ingestion rise in heat production. Recent work suggests the gut derived hormone secretin may play a key role in this effect, directly linking BAT activation to the alimentary tract. Not only gut hormones but also metabolites derived from gut microbiota such as butyrate may be an important activator of BAT during cold exposure. Additional regulatory factors include bone morphogenic proteins, fibroblast growth factor 21, Vascular endothelial growth factors and transient receptor potential vanilloid receptors which are important components of thermal sensing and hence how brown adipose tissue responds to the cold. In the future the main challenge is to understand how these regulatory factors combine with each other and with inhibitory factors to control heat production from BAT, and what their relative importance is in differing circumstances. Knocking out UCP1 has revealed other sources of heat production in BAT including creatine-dependent cycles and a futile cycle of Ca²⁺shuttling into and out of the endoplasmic reticulum via the SERCA and ryanodine receptors.

论文编号:	DOI:10.1016/j.mam.2019.07.005
论文题目:	Switching on the Furnace: Regulation of Heat Production in Brown Adipose Tissue
英文论文题目:	Switching on the Furnace: Regulation of Heat Production in Brown Adipose Tissue
第一作者:	Li Li, Baoguo Li, Min Li, John R. Speakman
英文第一作者:	Li Li, Baoguo Li, Min Li, John R. Speakman
联系作者:
英文联系作者:
外单位作者单位:
英文外单位作者单位:
发表年度:	2019-08-15
卷:
期:
页码:
摘要:	Endothermy requires a source of endogenous heat production. In birds, this is derived primarily from shivering, but in mammals it is mostly non-shivering thermogenesis (NST). Brown adipose tissue (BAT) is a specialized tissue found in Eutherian mammals that is the source of most NST. Heat production in BAT depends primarily on the activity of uncoupling protein 1 (UCP1), which decouples transport of protons across the inner mitochondrial membrane from synthesis of ATP. UCP1 and hence heat production of BAT is regulated by many factors. In this paper we discuss the main factors activating UCP1 and increasing heat production. Probably the most well-known activator is the catecholamine norepinephrine (NE) which is released from sympathetic nerve endings and binds to adrenergic receptors that are abundantly expressed on BAT. NE stimulates release of free-fatty acids. It was previously thought that such FFAs were essential for activation of UCP1. However recent work has suggested intracellular lipolysis is not essential and FFAs can be derived from extracellular sources. Thyroid hormones also exert impacts on metabolic rate via effects on brown adipocytes which express type 2 deiodinase. Knocking out DIO2 makes mice cold intolerant. Parathyroid hormone appears to also be a potent regulator of BAT activity and may be an important mediator of elevated expenditure during cancer cachexia, although this is disputed by observations that cachexia wasting is not blunted in UCP1 KO mice. Cardiac natriuretic peptides have also been implicated in regulating BAT thermogenesis and the interconversion of beige adipocytes from their white to brown form. Activation of BAT thermogenesis may be an important component of the post-ingestion rise in heat production. Recent work suggests the gut derived hormone secretin may play a key role in this effect, directly linking BAT activation to the alimentary tract. Not only gut hormones but also metabolites derived from gut microbiota such as butyrate may be an important activator of BAT during cold exposure. Additional regulatory factors include bone morphogenic proteins, fibroblast growth factor 21, Vascular endothelial growth factors and transient receptor potential vanilloid receptors which are important components of thermal sensing and hence how brown adipose tissue responds to the cold. In the future the main challenge is to understand how these regulatory factors combine with each other and with inhibitory factors to control heat production from BAT, and what their relative importance is in differing circumstances. Knocking out UCP1 has revealed other sources of heat production in BAT including creatine-dependent cycles and a futile cycle of Ca2+shuttling into and out of the endoplasmic reticulum via the SERCA and ryanodine receptors.
英文摘要:	Endothermy requires a source of endogenous heat production. In birds, this is derived primarily from shivering, but in mammals it is mostly non-shivering thermogenesis (NST). Brown adipose tissue (BAT) is a specialized tissue found in Eutherian mammals that is the source of most NST. Heat production in BAT depends primarily on the activity of uncoupling protein 1 (UCP1), which decouples transport of protons across the inner mitochondrial membrane from synthesis of ATP. UCP1 and hence heat production of BAT is regulated by many factors. In this paper we discuss the main factors activating UCP1 and increasing heat production. Probably the most well-known activator is the catecholamine norepinephrine (NE) which is released from sympathetic nerve endings and binds to adrenergic receptors that are abundantly expressed on BAT. NE stimulates release of free-fatty acids. It was previously thought that such FFAs were essential for activation of UCP1. However recent work has suggested intracellular lipolysis is not essential and FFAs can be derived from extracellular sources. Thyroid hormones also exert impacts on metabolic rate via effects on brown adipocytes which express type 2 deiodinase. Knocking out DIO2 makes mice cold intolerant. Parathyroid hormone appears to also be a potent regulator of BAT activity and may be an important mediator of elevated expenditure during cancer cachexia, although this is disputed by observations that cachexia wasting is not blunted in UCP1 KO mice. Cardiac natriuretic peptides have also been implicated in regulating BAT thermogenesis and the interconversion of beige adipocytes from their white to brown form. Activation of BAT thermogenesis may be an important component of the post-ingestion rise in heat production. Recent work suggests the gut derived hormone secretin may play a key role in this effect, directly linking BAT activation to the alimentary tract. Not only gut hormones but also metabolites derived from gut microbiota such as butyrate may be an important activator of BAT during cold exposure. Additional regulatory factors include bone morphogenic proteins, fibroblast growth factor 21, Vascular endothelial growth factors and transient receptor potential vanilloid receptors which are important components of thermal sensing and hence how brown adipose tissue responds to the cold. In the future the main challenge is to understand how these regulatory factors combine with each other and with inhibitory factors to control heat production from BAT, and what their relative importance is in differing circumstances. Knocking out UCP1 has revealed other sources of heat production in BAT including creatine-dependent cycles and a futile cycle of Ca2+shuttling into and out of the endoplasmic reticulum via the SERCA and ryanodine receptors.
刊物名称:	Molecular Aspects of Medicine
英文刊物名称:	Molecular Aspects of Medicine
论文全文:
英文论文全文:
全文链接:
其它备注:	Li Li, Baoguo Li, Min Li, John R. Speakman. Switching on the Furnace: Regulation of Heat Production in Brown Adipose Tissue. Molecular Aspects of Medicine. DOI:10.1016/j.mam.2019.07.005
英文其它备注:
学科:
英文学科:
影响因子:
第一作者所在部门:
英文第一作者所在部门:
论文出处:
英文论文出处:
论文类别:
英文论文类别:
参与作者:
英文参与作者: