Origins and early development of the concept that brown adipose tissue thermogenesis is linked to energy balance and obesity

Nicotine, the main addictive component of tobacco, promotes body weight reduction in humans and rodents. Recent evidence has suggested that nicotine acts in the central nervous system to modulate energy balance. Specifically, nicotine modulates hypothalamic AMP-activated protein kinase to decrease feeding and to increase brown adipose tissue thermogenesis through the sympathetic nervous system, leading to weight loss. Of note, most of this evidence has been obtained in animal models fed with normal diet or low-fat diet (LFD). However, its effectiveness in obese models remains elusive. Because obesity causes resistance towards many factors involved in energy homeostasis, the aim of this study has been to compare the effect of nicotine in a diet-induced obese (DIO) model, namely rats fed a high-fat diet, with rats fed a LFD. Our data show that chronic peripheral nicotine treatment reduced body weight by decreasing food intake and increasing brown adipose tissue thermogenesis in both LFD and DIO rats. This overall negative energy balance was associated to decreased activation of hypothalamic AMP-activated protein kinase in both models. Furthermore, nicotine improved serum lipid profile, decreased insulin serum levels, as well as reduced steatosis, inflammation, and endoplasmic reticulum stress in the liver of DIO rats but not in LFD rats. Overall, this evidence suggests that nicotine diminishes body weight and improves metabolic disorders linked to DIO and might offer a clear-cut strategy to develop new therapeutic approaches against obesity and its metabolic complications.

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Effects of ovarian hormones on energy balance and brown adipose tissue thermogenesis

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1986.250.2.r245 ◽

1986 ◽

Vol 250 (2) ◽

pp. R245-R249 ◽

Cited By ~ 17

Author(s):

D. Richard

Keyword(s):

Adipose Tissue ◽

Energy Balance ◽

Food Intake ◽

Energy Expenditure ◽

Brown Adipose Tissue ◽

Energy Intake ◽

Ovarian Hormones ◽

Ovariectomized Rats ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis

This study was carried out to investigate the nutritional energetics of ovariectomized rats with or without ovarian hormone replacement. Rats were divided into five groups: 1) sham operated, 2) ovariectomized, 3) ovariectomized and treated with progesterone, 4) ovariectomized and treated with estradiol, or 5) ovariectomized and treated with estradiol and progesterone. After 36 days of treatment, energy contents of all five groups were determined together with energy content of food and feces. Brown adipose tissue thermogenesis was assessed through mitochondrial GDP binding assay. Results show that ovariectomy leads to a 16% increase in metabolizable energy intake. This increase was accompanied by a twofold increase in body energy gain. Progesterone did not further affect energy intake and gain in ovariectomized rats. However, increases in both food intake and energy gain were prevented by the estradiol replacement therapy. There was no difference in energy expenditure between sham-operated and ovariectomized rats in the absence of estradiol. In estradiol-treated animals, energy expenditure (kJ.kg body wt-0.75 . day-1) showed a slight increase. There was no difference in protein content of interscapular brown adipose tissue between all five groups. GDP binding was slightly reduced in ovariectomized estradiol-treated rats. It is concluded from this study that ovarian hormones produce their effects on energy balance mainly by altering food intake.

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Energy balance and brown adipose tissue thermogenesis during pregnancy in Syrian hamsters

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1986.250.5.r845 ◽

1986 ◽

Vol 250 (5) ◽

pp. R845-R850 ◽

Cited By ~ 4

Author(s):

G. N. Wade ◽

G. Jennings ◽

P. Trayhurn

Keyword(s):

Adipose Tissue ◽

Energy Balance ◽

Food Intake ◽

Brown Adipose Tissue ◽

Interscapular Brown Adipose Tissue ◽

Estrous Cycles ◽

Syrian Hamsters ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis ◽

Circulating Levels

Energy balance and brown adipose tissue thermogenesis were examined during pregnancy in Syrian hamsters (Mesocricetus auratus). Neither estrous cycles nor pregnancy had any effect on food intake, but both were accompanied by significant changes in body weight. Despite their substantial weight gains (attributable to growth of fetuses and placentas), pregnant hamsters actually lost a mean of 48 kJ in carcass energy, whereas unmated controls gained 98 kJ over the same 15 days. During pregnancy hamsters exhibited an increase in protein deposition (almost entirely in the fetuses and placentas), but they lost nearly 40% of their body lipid. An apparent increase in energy expenditure occurred despite a highly significant decrease in brown adipose tissue thermogenesis during pregnancy. By day 15 of pregnancy (within 13 h of expected parturition) there were substantial decreases in interscapular brown adipose tissue weight (-59%), protein content (-54%), and cytochrome-c oxidase activity (-69%). These changes in brown adipose tissue were evident by day 4 of pregnancy and persisted through lactation. It is suggested that this suppression of brown adipose tissue function is due to increased circulating levels of prolactin and subsequently to the nutritional stress of conceptus growth in the absence of an increase in food intake.

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The role of brown adipose tissue thermogenesis in energy balance

New Perspectives in Adipose Tissue ◽

10.1016/b978-0-408-10857-7.50014-2 ◽

1985 ◽

pp. 199-222

Author(s):

Jean Himms-Hagen

Keyword(s):

Adipose Tissue ◽

Energy Balance ◽

Brown Adipose Tissue ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis

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Energy balance and brown adipose tissue thermogenesis during chronic endotoxemia in rats

Journal of Applied Physiology ◽

10.1152/jappl.1989.66.4.1970 ◽

1989 ◽

Vol 66 (4) ◽

pp. 1970-1975 ◽

Cited By ~ 5

Author(s):

J. Arnold ◽

R. A. Little ◽

N. J. Rothwell

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Energy Balance ◽

Energy Expenditure ◽

Brown Adipose Tissue ◽

Body Weight Gain ◽

Male Rats ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis

The effects of continuously administered endotoxin on 7-day energy balance were investigated in male rats. Three groups of rats were implanted with osmotic pumps; two groups received saline-filled pumps, whereas the third received endotoxin. One of the saline groups was pair fed to match the food intake of the endotoxemic rats. After 7 days, body energy and protein and fat contents of rats were determined together with the energy content of food and feces. Endotoxin infusion not only induced fever, but it also suppressed appetite and significantly decreased body weight gain. Metabolizable energy intake was reduced by approximately 20% in infected rats. Although protein and fat gains were lowest in the endotoxin group, there appeared to be a selective loss of protein when considered as percent of body weight. Percent body fat was unaltered between the groups. Energy expenditure considered in absolute (kJ) or body weight-independent (kJ/kg0.67) terms yielded similar patterns of results; expenditure (kJ) was 10 and 20% (P less than 0.05, P less than 0.01) lower in the endotoxemic and pair-fed rats, respectively, compared with controls. Hence, compared with pair-fed rats, endotoxin-infused animals had a 10% rise in their expenditure. Brown adipose tissue thermogenesis was assessed by mitochondrial binding of guanosine 5′-diphosphate, and results showed that binding was greatest in endotoxemic rats and lowest in the pair-fed animals. The present results suggest that in this endotoxemic model appetite suppression exacerbates changes in energy balance. However, the reduction in body weight gain is also dependent on a decrease in metabolic efficiency and an increase in total energy expenditure.(ABSTRACT TRUNCATED AT 250 WORDS)

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Central Pathways Controlling Brown Adipose Tissue Thermogenesis

Physiology ◽

10.1152/nips.01502.2003 ◽

2004 ◽

Vol 19 (2) ◽

pp. 67-74 ◽

Cited By ~ 26

Author(s):

Shaun F. Morrison

Keyword(s):

Adipose Tissue ◽

Energy Balance ◽

Body Temperature ◽

Brown Adipose Tissue ◽

Heat Production ◽

Functional Organization ◽

Sympathetic Outflow ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis ◽

Central Network

Heat production in brown adipose tissue contributes to cold defense, to stress-induced increases in body temperature, and to energy balance. Elucidating the functional organization of the central network controlling the sympathetic outflow to brown adipose tissue could provide a framework for understanding how dysregulation of thermogenesis contributes to hyperthermia and to obesity.

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A YY1 phosphorylation switch in brown adipose tissue orchestrates energy homeostasis.

10.21203/rs.3.rs-523586/v1 ◽

2021 ◽

Author(s):

Zyanya Díaz-Hirashi ◽

Tian Gao ◽

Chiara Scaffidi ◽

Monika Fey ◽

Susan Murray ◽

...

Keyword(s):

Adipose Tissue ◽

Energy Balance ◽

Brown Adipose Tissue ◽

Transcriptional Control ◽

Energy Homeostasis ◽

Whole Body ◽

Regulatory Subunit ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis

Abstract Whole-body energy homeostasis is influenced by anabolic and catabolic cellular programs, which depend on environmental and nutritional cues. Adipose tissue plays a predominant role in the physiological regulation of energy balance by either storing or consuming energy through brown adipose tissue thermogenesis. It is however not clearly understood how brown adipose tissue balances catabolic and anabolic states. We show here that the transcription factor YY1 senses energetic state through a post-translational S120 phosphorylation switch. Adrenergic signaling leads to YY1 dephosphorylation which directly activates thermogenesis and a catabolic gene program while its phosphorylation maintains an anabolic program. Mechanistically, YY1 dephosphorylation increases chromatin binding at distal genomic loci respective to the transcription start site but remains constitutively bound to TSS. This mode of transcriptional control influences the activating and repressive function of YY1 and regulates catabolism/anabolism. We show that YY1 interacts with PPP1R3B, a regulatory subunit of the phosphatase PP1 and that in vivo knockdown of PPP1R3B protects against diet-induced obesity and insulin resistance. Our results uncover a novel transcriptional mechanism of metabolism orchestrated by YY1 phosphorylation switch and identifies PPP1R3B as a regulator of energy balance.

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Glucagon-like peptide-1 regulates brown adipose tissue thermogenesis via the gut-brain axis in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00068.2018 ◽

2018 ◽

Vol 315 (4) ◽

pp. R708-R720 ◽

Cited By ~ 17

Author(s):

Jean-Philippe Krieger ◽

Ellen Paula Santos da Conceição ◽

Graciela Sanchez-Watts ◽

Myrtha Arnold ◽

Klaus G. Pettersen ◽

...

Keyword(s):

Adipose Tissue ◽

Energy Balance ◽

Brown Adipose Tissue ◽

Body Weight Gain ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis ◽

Sympathetic Regulation ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Endogenous intestinal glucagon-like peptide-1 (GLP-1) controls satiation and glucose metabolism via vagal afferent neurons (VANs). Recently, VANs have received increasing attention for their role in brown adipose tissue (BAT) thermogenesis. It is, however, unclear whether VAN GLP-1 receptor (GLP-1R) signaling affects BAT thermogenesis and energy expenditure (EE) and whether this VAN mechanism contributes to energy balance. First, we tested the effect of the GLP-1R agonist exendin-4 (Ex4, 0.3 μg/kg ip) on EE and BAT thermogenesis and whether these effects require VAN GLP-1R signaling using a rat model with a selective Glp1r knockdown (kd) in VANs. Second, we examined the role of VAN GLP-1R in energy balance during chronic high-fat diet (HFD) feeding in VAN Glp1r kd rats. Finally, we used viral transsynaptic tracers to identify the possible neuronal substrates of such a gut-BAT interaction. VAN Glp1r kd attenuated the acute suppressive effects of Ex4 on EE and BAT thermogenesis. Consistent with this finding, the VAN Glp1r kd increased EE and BAT activity, diminished body weight gain, and improved insulin sensitivity compared with HFD-fed controls. Anterograde transsynaptic viral tracing of VANs infected major hypothalamic and hindbrain areas involved in BAT sympathetic regulation. Moreover, retrograde tracing from BAT combined with laser capture microdissection revealed that a population of VANs expressing Glp1r is synaptically connected to the BAT. Our findings reveal a novel role of VAN GLP-1R signaling in the regulation of EE and BAT thermogenesis and imply that through this gut-brain-BAT connection, intestinal GLP-1 plays a role in HFD-induced metabolic syndrome.

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