POSSIBLE STIMULATION OF THERMOGENESIS IN BROWN ADIPOSE TISSUE BY THYROID-STIMULATING HORMONE

doi:10.1016/S0140-6736(75)90061-6

The Lancet

Volume 306, Issue 7926, 26 July 1975, Pages 160-161

https://doi.org/10.1016/S0140-6736(75)90061-6 Get rights and content

Abstract

It is suggested that in addition to stimulating the thyroid gland (i.e., the main regulator of metabolic-rate in adults) thyroid-stimulating hormone (T.S.H.) stimulates the second thermoregulatory organ (i.e., the brown adipose tissue). Brown fat functions as a thermogenic organ in hibernating animals, in newborn infants, and during cold acclimatisation. However, B.F. may persist in childhood and in some adults. Its hypertrophy in response to T.S.H. could account for certain unexplained features of myxœdema in which serum-T.S.H. is raised, such as swelling of the supraclavicular fat pad and the less commonly encountered symptoms of ascites or pericardial and pleural serous effusions which can persist for years in undiagnosed cases and respond rapidly to thyroxine when serum-T.S.H. returns to normal. Lack of thyroxine is not the cause of these features since they are not found in pituitary myxœdema, where thyroid hormone levels are as low but T.S.H. is absent.

References (21)

T. Flatmark et al.
Rev. Bioenergetics
(1975)
Y. Sachdev et al.
Lancet
(1975)
D. Doniach et al.
Clins Endocr. Metab.
(1975)
R.E. Smith et al.
Physiol. Rev.
(1969)
H. Baum
The Cell in Medical Science
W.H. Florsheim
H. Ikemoto et al.
Jap. J. Physiol.
(1967)
D.W. Fawcett et al.
Endocrinology
(1949)
A. Kuroshima et al.
Jap. J. Physiol.
(1967)
G. Steiner et al.
Clin. J. Physiol. Pharmac.
(1968)

There are more references available in the full text version of this article.

Cited by (17)

Targeting white, brown and perivascular adipose tissue in atherosclerosis development
2017, European Journal of Pharmacology
Citation Excerpt :
Activation of the β3-adrenergic receptors is the most well-known and potent way to induce thermogenesis and lipid combustion (Cannon and Nedergaard, 2004; Cypess et al., 2015) and β3-adrenergic receptor agonists such as CL-316243 potently induce lipid uptake by BAT (Berbée et al., 2015). In humans, cold (van der Lans et al., 2013; Yoneshiro et al., 2013), activation of transient receptor potential channels by capsinoids (Yoneshiro et al., 2012) and thyroid hormones (Broeders et al., 2016; Doniach, 1975) have been demonstrated to activate BAT. To date, it has not been established that BAT activation lowers plasma triglyceride levels in humans, likely because most studies have applied cold exposure that increases hepatic VLDL-triglyceride production in addition to enhancing triglyceride clearance (Hoeke & Nahon et al., unpublished).
Obesity is a well-established risk factor for atherosclerosis. However, the mechanistic link between accumulation of adipose tissue and development of atherosclerosis is not clear. Adipose tissue comprises various depots including white adipose tissue (WAT), brown adipose tissue (BAT) and thoracic and abdominal perivascular adipose tissue (PVAT). The phenotype of thoracic PVAT resembles BAT, whereas abdominal PVAT is more like WAT. Here, we review the distinct roles of the adipose tissue depots in the development of atherosclerosis with the ultimate aim to understand how these can be targeted to reduce atherosclerosis. In obesity, increased fatty acid release by WAT and decreased lipid combustion by BAT and thoracic PVAT lead to hyperlipidaemia, which contributes to atherosclerosis development. Besides, obese WAT and abdominal PVAT release pro-inflammatory factors that further promote atherosclerosis. To discourage atherosclerosis development, strategies that reduce the release of pro-inflammatory factors and fatty acids from WAT and abdominal PVAT, or increase combustion of fatty acids by activation of BAT and thoracic PVAT and beiging of WAT are probably most efficient. Possible therapies could include anti-inflammatory compounds such as adiponectin and salicylates to lower inflammation, and β3-adrenergic receptor activators to increase fatty acid combustion. Additional and more specific strategies to promote fatty acid combustion are currently subject of investigation. In conclusion, different adipose depots differentially affect atherosclerosis development, in which atherosclerosis is promoted by energy-storing adipose depots and attenuated by energy-combusting adipose tissue. In obesity, combining therapies that reduce inflammation and increase combustion of lipids are most conceivable to restrain atherogenesis.
Effects of growth hormone on uncoupling protein 1 in white adipose tissues in obese mice
2017, Growth Hormone and IGF Research
Citation Excerpt :
Brown adipose tissue (BAT) contributes significantly to the control of body temperature and energy expenditure in rodents and hibernating animals [1].
The transition of white adipocytes to beige cells (a phenomenon referred to as browning or beigeing) during obesity has been previously reported. Our study aimed to examine the mechanisms through which obesity induced by a high fat diet (HFD) affects uncoupling protein 1 (UCP1) expression via signal transduction and activator of transcription 5 (STAT5s).
Seven-week-old male C57BL/6J mice were fed a normal or HFD for 11 weeks. Body weight, white adipose tissue weight, and blood lipid and glucose levels were measured. To unveil the molecular mechanisms of UCP1 expression in adipose tissue, we performed further studying 3T3-L1 cells using qRT-PCR. We also measured UCP1 promoter activity in the TSA201 cell line using a dual luciferase assay. In addition, we analyzed the predicted consensus sequences for STAT5 binding in the UCP1 promoter region.
Mice fed an HFD had higher body weight and intra-abdominal adipose tissues weight and a higher expression of UCP1, GH receptor (GHR), STATs, suppressors of cytokine signaling (SOCSs), and cytokine-inducible SH2-containing protein (CISH) compared to control mice. In 3T3-L1 cell studies, GH induced phosphorylation of the STAT5, SOCSs, CISH and UCP1 expressions. UCP1 promoter activity was associated with constitutively active STAT5 in a dose-dependent manner. We confirmed functional STAT5 binding sites at − 425, − 279, and − 178 bp of the UCP1 promoter.
We suggest that endogenous GH induces UCP1 expression in adipose tissue via STAT5.
Sudden infant death syndrome: A hypothesis
1997, Medical Hypotheses
A study of the strikingly low incidence of sudden infant death syndrome in Eastern countries revealed significant differences in infant handling thought to have an etiological bearing; therefore this writer suggested that adoption of certain Eastern methods of nursing may reduce the incidence of sudden infant death syndrome. A dramatic fall in incidence has resulted from implementing one of the suggestions made by the writer in 1983, namely the abandonment of the prone position, after initial opposition. The present hypothesis sets out to give a scientific explanation for this fall, and is a unified hypothesis explaining certain puzzling and disparate features of sudden infant death syndrome such as the remarkable winter incidence, age incidence, and the occurrence of sudden infant death syndrome during sleep, and is based on a postulated disturbance in thermoregulatory function (a unique hypothermia). Recomendations are made for evolving a test for sudden infant death syndrome-proneness and a possible method of treatment of a fatality within a short time frame.
Diet-induced thermogenesis
1982, Pharmacology and Therapeutics
The Brown Fat Cell
1982, International Review of Cytology
Brown fat cells produce heat by oxidation of the fatty acids. Isolated cells are prepared by collagenase treatment of brown fat from hamsters and rats. The chapter outlines the isolation procedure for the brown fat cells and discusses the properties of the isolated cell suspension. The effect of the incubation conditions on the parameters such as membrane potential, lipolysis, and respiration as an indirect measure of thermogenesis are studied. Brown fat thermogenesis in vivo is stimulated by norepinephrine (NE), liberated from sympathetic nerve endings in the tissue. The hormones studied on brown fat cells can be divided into three major groups—namely, (1) the hormones that exert their effect on the brown fat cell itself; (2) the hormones that act solely by releasing stored catecholamines, within the tissue or in impure cell preparations; and (3) the hormones that only affect the tissue indirectly in the intact animal. The fatty acids released by hormone-sensitive lipase activity may be exported either as such, or activated to acyl coenzyme A (acyl-CoA) in the cell. The acetyl coenzyme A (acetyl-CoA), produced by mitochondrial β-oxidation, is further metabolized by different mitochondrial matrix enzymes. The chapter also discusses the mechanism of heat production in the brown fat cell.
Thyrotropin receptors in adipose tissue, retro-orbital tissue and lymphocytes
1978, Molecular and Cellular Endocrinology
Thyrotropin (TSH) receptors on retro-orbital muscle and fat have been implicated in the pathogenesis of Graves' exophthalmos and it has been suggested that TSH has a direct effect on human fat metabolism. We have therefore investigated the interaction of biologically active ¹²⁵I-labelled TSH with membranes prepared from human adipose, retro-orbital and thyroid tissue. Since lymphocytes contain receptors for several polypeptide hormones, TSH binding to lymphocyte membranes was also studied.
We were unable to demonstrate TSH receptors in adult human adipose tissue, retro-orbital muscle and fat, or peripheral blood lymphocytes. In contrast, adult and neonatal guinea pig adipose tissue membranes showed similar TSH binding characteristics to guinea pig thyroid membranes.

View all citing articles on Scopus

View full text

HypothesisPOSSIBLE STIMULATION OF THERMOGENESIS IN BROWN ADIPOSE TISSUE BY THYROID-STIMULATING HORMONE

Abstract

Rev. Bioenergetics

Lancet

Clins Endocr. Metab.

Physiol. Rev.

The Cell in Medical Science

Jap. J. Physiol.

Endocrinology

Jap. J. Physiol.

Clin. J. Physiol. Pharmac.

Hypothesis
POSSIBLE STIMULATION OF THERMOGENESIS IN BROWN ADIPOSE TISSUE BY THYROID-STIMULATING HORMONE