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

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.

scholarly journals Median preoptic area neurons are required for the cooling and febrile activations of brown adipose tissue thermogenesis in rat

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ellen Paula Santos da Conceição ◽  
Shaun F. Morrison ◽  
Georgina Cano ◽  
Pierfrancesco Chiavetta ◽  
Domenico Tupone
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Energy Homeostasis ◽  
Preoptic Area ◽  
Therapeutic Approaches ◽  
Dorsomedial Hypothalamus ◽  
Brown Adipose ◽  
Brown Adipose Tissue Thermogenesis

Abstract Within the central neural circuitry for thermoregulation, the balance between excitatory and inhibitory inputs to the dorsomedial hypothalamus (DMH) determines the level of activation of brown adipose tissue (BAT) thermogenesis. We employed neuroanatomical and in vivo electrophysiological techniques to identify a source of excitation to thermogenesis-promoting neurons in the DMH that is required for cold defense and fever. Inhibition of median preoptic area (MnPO) neurons blocked the BAT thermogenic responses during both PGE2-induced fever and cold exposure. Disinhibition or direct activation of MnPO neurons induced a BAT thermogenic response in warm rats. Blockade of ionotropic glutamate receptors in the DMH, or brain transection rostral to DMH, blocked cold-evoked or NMDA in MnPO-evoked BAT thermogenesis. RNAscope technique identified a glutamatergic population of MnPO neurons that projects to the DMH and expresses c-Fos following cold exposure. These discoveries relative to the glutamatergic drive to BAT sympathoexcitatory neurons in DMH augment our understanding of the central thermoregulatory circuitry in non-torpid mammals. Our data will contribute to the development of novel therapeutic approaches to induce therapeutic hypothermia for treating drug-resistant fever, and for improving glucose and energy homeostasis.

Fat feeding causes widespread in vivo insulin resistance, decreased energy expenditure, and obesity in rats

1986 ◽  
Vol 251 (5) ◽  
pp. E576-E583 ◽  
Author(s):  
L. H. Storlien ◽  
D. E. James ◽  
K. M. Burleigh ◽  
D. J. Chisholm ◽  
E. W. Kraegen
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Metabolic Rate ◽  
Brown Adipose Tissue ◽  
Whole Body ◽  
Brown Adipose ◽  
Glucose Output ◽  
Fat Feeding

High levels of dietary fat may contribute to both insulin resistance and obesity in humans but evidence is limited. The euglycemic clamp technique combined with tracer administration was used to study insulin action in vivo in liver and individual peripheral tissues after fat feeding. Basal and nutrient-stimulated metabolic rate was assessed by open-circuit respirometry. Adult male rats were pair-fed isocaloric diets high in either carbohydrate (69% of calories; HiCHO) or fat (59% of calories; HiFAT) for 24 +/- 1 days. Feeding of the HiFAT diet resulted in a greater than 50% reduction in net whole-body glucose utilization at midphysiological insulin levels (90-100 mU/l) due to both reduced glucose disposal and, to a lesser extent, failure to suppress liver glucose output. Major suppressive effects of the HiFAT diet on glucose uptake were found in oxidative skeletal muscles (29-61%) and in brown adipose tissue (BAT; 78-90%), the latter accounting for over 20% of the whole-body effect. There was no difference in basal metabolic rate but thermogenesis in response to glucose ingestion was higher in the HiCHO group. In contrast to their reduced BAT weight, the HiFAT group accumulated more white adipose tissue, consistent with reduced energy expenditure. HiFAT feeding also resulted in major decreases in basal and insulin-stimulated conversion of glucose to lipid in liver (26-60%) and brown adipose tissue (88-90%) with relatively less effect in white adipose (0-43%). We conclude that high-fat feeding results in insulin resistance due mainly to effects in oxidative skeletal muscle and BAT.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Nicotine Improves Obesity and Hepatic Steatosis and ER Stress in Diet-Induced Obese Male Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (5) ◽  
pp. 1679-1689 ◽  
Author(s):  
Patricia Seoane-Collazo ◽  
Pablo B. Martínez de Morentin ◽  
Johan Fernø ◽  
Carlos Diéguez ◽  
Rubén Nogueiras ◽  
...  
Keyword(s):  
Nervous System ◽  
Body Weight ◽  
Adipose Tissue ◽  
Energy Balance ◽  
Protein Kinase ◽  
Brown Adipose Tissue ◽  
Male Rats ◽  
Brown Adipose ◽  
Brown Adipose Tissue Thermogenesis ◽  
Amp Activated Protein Kinase

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.

Activation of brown adipose tissue thermogenesis in recovery from anesthetic hypothermia in rats

1991 ◽  
Vol 261 (2) ◽  
pp. R301-R304 ◽  
Author(s):  
Y. Shimizu ◽  
M. Saito
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Rectal Temperature ◽  
Recovery Phase ◽  
Adrenergic Blockade ◽  
Appreciable Change ◽  
Brown Adipose ◽  
Steady Level ◽  
Brown Adipose Tissue Thermogenesis

Changes of brown adipose tissue (BAT) thermogenesis in the recovery from anesthetic hypothermia were studied by measuring the temperatures of the interscapular BAT and rectum or the tissue uptake of 2-deoxyglucose (2-DG) in rats. After intraperitoneal injection of pentobarbital sodium (50 mg/kg), rectal temperature decreased to reach a steady level of approximately 33 degrees C (steady phase) and then increased gradually (recovery phase). The temperature of the interscapular BAT was significantly higher than rectal temperature in the recovery phase. The uptake of 2-DG in vivo in BAT was low in the steady phase but increased greatly in the recovery phase. The increase in 2-DG uptake was suppressed after surgical sympathetic denervation or when rectal temperature was maintained at approximately 37.5 degrees C. In the heart, skeletal muscle, and white adipose tissue, there was no appreciable change in 2-DG uptake except a slight increase in the heart. beta-Adrenergic blockade attenuated the changes in BAT temperature and 2-DG uptake seen during the recovery phase. It was concluded that BAT significantly contributes to heat production in recovery from anesthetic hypothermia.

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

1986 ◽  
Vol 250 (2) ◽  
pp. R245-R249 ◽  
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.

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

1986 ◽  
Vol 250 (5) ◽  
pp. R845-R850 ◽  
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.

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

1989 ◽  
Vol 66 (4) ◽  
pp. 1970-1975 ◽  
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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