Leptin increases uncoupling protein expression and energy expenditure

1997 ◽  
Vol 273 (1) ◽  
pp. E226-E230 ◽  
Author(s):  
P. J. Scarpace ◽  
M. Matheny ◽  
B. H. Pollock ◽  
N. Tumer
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Food Consumption ◽  
Uncoupling Protein ◽  
Mrna Levels ◽  
Sympathetic Outflow ◽  
Brown Adipose ◽  
Ad Libitum

In ob/ob mice, leptin increases energy expenditure and sympathetic outflow to brown adipose tissue (BAT). To test whether the mechanism of increased energy expenditure may involve increased thermogenesis in BAT, we acclimated normal rats to thermoneutrality for 2 wk followed by leptin administration for 1 wk. Some rats were food restricted for 1 wk to the level of food consumption in the leptin-treated ad libitum-fed rats, and the same rats were both food restricted and administered leptin for a second week. We examined oxygen consumption and uncoupling protein (UCP) expression in BAT. Leptin increased oxygen consumption after the 5th and 6th days in ad libitum-fed rats and after the 4th, 5th, and 6th days in food-restricted rats. Leptin increased BAT UCP mRNA levels greater than twofold in both ad libitum-fed and food-restricted rats. These data demonstrate a leptin-induced increase in energy expenditure in nonmutant rodents and suggest that one mechanism by which leptin increases energy expenditure is through increased thermogenesis in BAT, including increased expression of UCP.

scholarly journals Postnatal selective suppression of lipoprotein lipase gene expression in brown adipose tissue (relative to the expression of the gene for the uncoupling protein) is not due to adrenergic insensitivity: a possible specific inhibitory effect of colostrum

1996 ◽  
Vol 314 (1) ◽  
pp. 261-267 ◽  
Author(s):  
María-Jesus OBREGÓN ◽  
Barbara CANNON ◽  
Jan NEDERGAARD
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Uncoupling Protein ◽  
Mrna Levels ◽  
Selective Suppression ◽  
Brown Adipose ◽  
Adrenergic Antagonist ◽  
Lpl Gene

The levels of mRNA coding for the uncoupling protein (UCP) and for lipoprotein lipase (LPL) were monitored in the brown adipose tissue of newborn rat pups. At 5 h after birth, the mRNA levels of UCP and LPL were high in pups exposed singly to 28 °C and low in pups kept singly at thermoneutrality (36 °C); in pups staying with the dam, the UCP mRNA levels were intermediate. However, the LPL mRNA levels were lower in pups staying with the dam than in pups at 36 °C, implying that factors additional to environmental temperature influenced LPL gene expression. Injection of noradrenaline into pups at thermoneutrality (36 °C) led to increases in UCP and LPL gene expression, but noradrenaline injections had no further effect in cold-exposed pups. The adrenergic effects were mediated via β-adrenergic receptors. The cold-induced increases in both UCP and LPL gene expression were abolished by the β-adrenergic antagonist propranolol. Thus differences in adrenergic responsiveness could not explain the differential expression of the UCP and LPL genes observed in pups staying with the dam. The presence of a physiological suppressor was examined by feeding single pups at 28 °C with different foods: nothing, water, Intralipid, cow's milk, rat milk and rat colostrum. None of these agents led to suppression of UCP gene expression, but colostrum led to a selective suppression of LPL gene expression. It was concluded that the genes for UCP and LPL were responsive to adrenergic stimuli immediately after birth, and it is suggested that a component of rat colostrum can selectively suppress LPL gene expression.

scholarly journals ChREBP-β regulates thermogenesis in brown adipose tissue

2020 ◽  
Vol 245 (3) ◽  
pp. 343-356 ◽  
Author(s):  
Chunchun Wei ◽  
Xianhua Ma ◽  
Kai Su ◽  
Shasha Qi ◽  
Yuangang Zhu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Uncoupling Protein ◽  
Critical Role ◽  
Active Form ◽  
Negative Regulator ◽  
Mrna Levels ◽  
Brown Adipose ◽  
Metabolic Remodeling

Brown adipose tissue (BAT) plays a critical role in energy expenditure by uncoupling protein 1 (UCP1)-mediated thermogenesis. Carbohydrate response element-binding protein (ChREBP) is one of the key transcription factors regulating de novo lipogenesis (DNL). As a constitutively active form, ChREBP-β is expressed at extremely low levels. Up to date, its functional relevance in BAT remains unclear. In this study, we show that ChREBP-β inhibits BAT thermogenesis. BAT ChREBP-β mRNA levels were elevated upon cold exposure, which prompted us to generate a mouse model overexpressing ChREBP-β specifically in BAT using the Cre/LoxP approach. ChREBP-β overexpression led to a whitening phenotype of BAT at room temperature, as evidenced by increased lipid droplet size and decreased mitochondrion content. Moreover, BAT thermogenesis was inhibited upon acute cold exposure, and its metabolic remodeling induced by long-term cold adaptation was significantly impaired by ChREBP-β overexpression. Mechanistically, ChREBP-β overexpression downregulated expression of genes involved in mitochondrial biogenesis, autophagy, and respiration. Furthermore, thermogenic gene expression (e.g. Dio2, UCP1) was markedly inhibited in BAT by the overexpressed ChREBP-β. Put together, our work points to ChREBP-β as a negative regulator of thermogenesis in brown adipocytes.

Effects of exposure temperature on brown adipose tissue uncoupling protein mRNA levels

1989 ◽  
Vol 67 (2-3) ◽  
pp. 147-151 ◽  
Author(s):  
Karl B. Freeman ◽  
Michael Heffernan ◽  
Zenobia Dhalla ◽  
Hasmukh V. Patel
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Effect Of Temperature ◽  
Initial Time ◽  
Maximal Response ◽  
Mrna Levels ◽  
Exposure Temperature ◽  
Brown Adipose ◽  
Uncoupling Protein Mrna

The effect of temperature on the amount of uncoupling protein mRNA in rat brown adipose tissue was examined after 1 and 14 days of exposure to cold. The relative amounts after 1 day, compared with rats kept at a thermoneutral temperature of 28 °C, were 3.2 at 19 °C, 3.3 at 11 °C, and 2.1 at 3 °C. This suggests that in warm-acclimated rats, a maximal response to a cold stimulus in brown adipose tissue is reached by 19 °C. In contrast to these results, the relative amounts of uncoupling protein mRNA after 14 days of cold exposure, compared with rats left at 28 °C, were 1.2 at 19 °C, 1.9 at 11 °C, and 2.1 at 3 °C. Since it is known that the amount of uncoupling protein in cold-acclimated rats increases continuously with decrease in temperature, the amount of protein reflects the mRNA levels during later times but not the initial time of exposure to cold.Key words: brown adipose tissue, uncoupling protein mRNA.

Plasticity in food intake, thermogenesis and body mass in the tree shrew (Tupaia belangeri) is affected by food restriction and refeeding

2016 ◽  
Vol 66 (2) ◽  
pp. 201-217 ◽  
Author(s):  
Wen-rong Gao ◽  
Wan-long Zhu ◽  
Fang-yan Ye ◽  
Mu-lin Zuo ◽  
Zheng-kun Wang
Keyword(s):  
Adipose Tissue ◽  
Food Intake ◽  
Brown Adipose Tissue ◽  
Body Mass ◽  
Food Restriction ◽  
Uncoupling Protein ◽  
Tissue Mass ◽  
Serum Leptin ◽  
Brown Adipose ◽  
Ad Libitum

Physiological adjustments are important strategies for small mammals in response to variation in food availability. To determine the physiological mechanisms affected by food restriction and refeeding, tree shrews were restricted to 85% of initial food intake for 4 weeks and refedad libitumfor another 4 weeks. Changes in food intake, body mass, thermogenesis, body composition, mitochondrial cytochromecoxidase activity, uncoupling protein-1 content in brown adipose tissue and serum leptin levels were measured. The results showed that body mass, body fat mass and serum leptin levels significantly decreased in food restricted tree shrews, and increased when the restriction ended, showing a short “compensatory growth” rather than over-weight or obesity compared withad libitumcontrols. Resting metabolic rate, non-shivering thermogenesis, brown adipose tissue mass (mg), and uncoupling protein-1 content decreased significantly in response to food restriction, and returned to the control levels after the animals were refedad libitum, while the brown adipose tissue mass (%) and cytochromecoxidase activity remained stable during food restriction and refeeding. Food intake increased shortly after refeeding, which perhaps contributed to the rapid regaining of body mass. These results suggest thatTupaia belangerican adjust the status of its physiology integratively to cope with the lack of food by means of decreasing body mass, thermogenesis and serum leptin levels. Leptin may act as a starvation signal to predominantly mediate the reduction in body mass and energy expenditure.

scholarly journals A Change in Liver Metabolism but Not in Brown Adipose Tissue Thermogenesis Is an Early Event in Ovariectomy-Induced Obesity in Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 2881-2891 ◽  
Author(s):  
Mariana Nigro ◽  
Anderson T. Santos ◽  
Clarissa S. Barthem ◽  
Ruy A. N. Louzada ◽  
Rodrigo S. Fortunato ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Brown Adipose Tissue ◽  
Glucose Homeostasis ◽  
Uncoupling Protein ◽  
Tolerance Test ◽  
Uncoupling Protein 1 ◽  
Ovx Rats ◽  
Bat Mitochondria ◽  
Brown Adipose

Menopause is associated with increased visceral adiposity and disrupted glucose homeostasis, but the underlying molecular mechanisms related to these metabolic changes are still elusive. Brown adipose tissue (BAT) plays a key role in energy expenditure that may be regulated by sexual steroids, and alterations in glucose homeostasis could precede increased weight gain after ovariectomy. Thus, the aim of this work was to evaluate the metabolic pathways in both the BAT and the liver that may be disrupted early after ovariectomy. Ovariectomized (OVX) rats had increased food efficiency as early as 12 days after ovariectomy, which could not be explained by differences in feces content. Analysis of isolated BAT mitochondria function revealed no differences in citrate synthase activity, uncoupling protein 1 expression, oxygen consumption, ATP synthesis, or heat production in OVX rats. The addition of GDP and BSA to inhibit uncoupling protein 1 decreased oxygen consumption in BAT mitochondria equally in both groups. Liver analysis revealed increased triglyceride content accompanied by decreased levels of phosphorylated AMP-activated protein kinase and phosphorylated acetyl-CoA carboxylase in OVX animals. The elevated expression of gluconeogenic enzymes in OVX and OVX + estradiol rats was not associated with alterations in glucose tolerance test or in serum insulin but was coincident with higher glucose disposal during the pyruvate tolerance test. Although estradiol treatment prevented the ovariectomy-induced increase in body weight and hepatic triglyceride and cholesterol accumulation, it was not able to prevent increased gluconeogenesis. In conclusion, the disrupted liver glucose homeostasis after ovariectomy is neither caused by estradiol deficiency nor is related to increased body mass.

scholarly journals Brown Adipose Tissue and Its Role in Insulin and Glucose Homeostasis

2021 ◽  
Vol 22 (4) ◽  
pp. 1530
Author(s):  
Katarzyna Maliszewska ◽  
Adam Kretowski
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Glucose Homeostasis ◽  
Uncoupling Protein ◽  
Negative Energy ◽  
Metabolic Complications ◽  
Brown Adipose ◽  
Prevalence Of Obesity

The increased worldwide prevalence of obesity, insulin resistance, and their related metabolic complications have prompted the scientific world to search for new possibilities to combat obesity. Brown adipose tissue (BAT), due to its unique protein uncoupling protein 1 (UPC1) in the inner membrane of the mitochondria, has been acknowledged as a promising approach to increase energy expenditure. Activated brown adipocytes dissipate energy, resulting in heat production. In other words, BAT burns fat and increases the metabolic rate, promoting a negative energy balance. Moreover, BAT alleviates metabolic complications like dyslipidemia, impaired insulin secretion, and insulin resistance in type 2 diabetes. The aim of this review is to explore the role of BAT in total energy expenditure, as well as lipid and glucose homeostasis, and to discuss new possible activators of brown adipose tissue in humans to treat obesity and metabolic disorders.

scholarly journals Postnatal recruitment of brown adipose tissue is induced by the cold stress experienced by the pups. An analysis of mRNA levels for thermogenin and lipoprotein lipase

1989 ◽  
Vol 259 (2) ◽  
pp. 341-346 ◽  
Author(s):  
M J Obregón ◽  
A Jacobsson ◽  
T Kirchgessner ◽  
M C Schotz ◽  
B Cannon ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cold Stress ◽  
Brown Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Uncoupling Protein ◽  
Mrna Levels ◽  
Rat Pups ◽  
Brown Adipose ◽  
Actin Mrna ◽  
Clear Increase

In order to investigate the postnatal recruitment process, gene expression in the brown adipose tissue of rat pups was followed during the first 20 h of life. In normal pups, the level of mRNA coding for the uncoupling protein thermogenin increased markedly but gradually within the first 24 h. Lipoprotein lipase and actin mRNA levels were relatively low and remained constant. In pups exposed to thermoneutral temperature (35 degrees C) for the first 12 h after birth, no increase in thermogenin mRNA or lipoprotein lipase mRNA was observed, whereas in pups exposed to 28 degrees C a clear increase in both thermogenin and lipoprotein lipase mRNA levels was found. Actin mRNA levels were not affected by the environmental temperature under these circumstances. It was concluded that the postnatal recruitment in brown adipose tissue is a consequence of the cold stress experienced by the newborn pups. Thus, postnatal recruitment is not ontogenically predetermined.

Mitochondrial proton leak in brown adipose tissue mitochondria of Ucp1-deficient mice is GDP insensitive

1999 ◽  
Vol 276 (6) ◽  
pp. E1073-E1082 ◽  
Author(s):  
Shadi Monemdjou ◽  
Leslie P. Kozak ◽  
Mary-Ellen Harper
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Proton Leak ◽  
Control Analysis ◽  
Mitochondrial Uncoupling ◽  
Bat Mitochondria ◽  
Brown Adipose ◽  
Deficient Mice

Mice deficient in mitochondrial uncoupling protein (UCP) 1 are cold sensitive, despite abundant expression of the homologues, Ucp2 and Ucp3 (S. Enerbäck, A. Jacobsson, E. M. Simpson, C. Guerra, H. Yamashita, M.-E. Harper, and L. P. Kozak. Nature 387: 90–94, 1997). We have analyzed characteristics of mitochondrial proton leak from brown adipose tissue (BAT) of Ucp1-deficient mice and normal controls and conducted the first top-down metabolic control analysis of oxidative phosphorylation in BAT mitochondria. Because purine nucleotides inhibit UCP1 and because UCP2 and the long form of UCP3 have putative purine nucleotide-binding regions, we predicted that proton leak in BAT mitochondria from Ucp1-deficient mice would be sensitive to GDP. On the contrary, although control over mitochondrial oxygen consumption and proton leak reactions at state 4 are strongly affected by 1 mM GDP in mitochondria from normal mice, there is no effect in UCP1-deficient mitochondria. In the presence of GDP, the overall kinetics of proton leak were not significantly different between Ucp1-deficient mice and controls. In its absence, state 4 respiration in normal BAT mitochondria was double that in its presence. Leak-dependent oxygen consumption was higher over a range of membrane potentials in its absence than in its presence. Thus proton leak, potentially including that through UCP2 and UCP3, is GDP insensitive. However, our measurements were made in the presence of albumin and may not allow for the detection of any fatty acid-induced UCP-mediated leak; this possibility requires investigation.

scholarly journals Leptin Modulates the Response of Brown Adipose Tissue to Negative Energy Balance: Implication of the GH/IGF-I Axis

2021 ◽  
Vol 22 (6) ◽  
pp. 2827
Author(s):  
Vicente Barrios ◽  
Laura M. Frago ◽  
Sandra Canelles ◽  
Santiago Guerra-Cantera ◽  
Eduardo Arilla-Ferreiro ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Balance ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Negative Energy ◽  
Negative Energy Balance ◽  
Cytokine Signaling ◽  
Mrna Levels ◽  
Brown Adipose ◽  
Igf I

The growth hormone (GH)/insulin-like growth factor I (IGF-I) axis is involved in metabolic control. Malnutrition reduces IGF-I and modifies the thermogenic capacity of brown adipose tissue (BAT). Leptin has effects on the GH/IGF-I axis and the function of BAT, but its interaction with IGF-I and the mechanisms involved in the regulation of thermogenesis remains unknown. We studied the GH/IGF-I axis and activation of IGF-I-related signaling and metabolism related to BAT thermogenesis in chronic central leptin infused (L), pair-fed (PF), and control rats. Hypothalamic somatostatin mRNA levels were increased in PF and decreased in L, while pituitary GH mRNA was reduced in PF. Serum GH and IGF-I concentrations were decreased only in PF. In BAT, the association between suppressor of cytokine signaling 3 and the IGF-I receptor was reduced, and phosphorylation of the IGF-I receptor increased in the L group. Phosphorylation of Akt and cyclic AMP response element binding protein and glucose transporter 4 mRNA levels were increased in L and mRNA levels of uncoupling protein-1 (UCP-1) and enzymes involved in lipid anabolism reduced in PF. These results suggest that modifications in UCP-1 in BAT and changes in the GH/IGF-I axis induced by negative energy balance are dependent upon leptin levels.

Corticosterone inhibits uncoupling protein gene expression in brown adipose tissue

1993 ◽  
Vol 265 (1) ◽  
pp. E81-E87 ◽  
Author(s):  
A. Moriscot ◽  
R. Rabelo ◽  
A. C. Bianco
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Adrenergic Stimulation ◽  
Brown Adipose ◽  
Adrenalectomized Rats ◽  
Intact Rats

Uncoupling protein (UCP) mRNA levels were studied in the interscapular brown adipose tissue (BAT) of rats undergoing different manipulations of the adrenal function and BAT adrenergic stimulation. Adrenalectomy did not affect UCP mRNA levels for up to 8 days post-surgery. However, adrenalectomized rats underwent a greater increase in UCP mRNA levels (26%) than intact rats after 4 h of cold exposure. Administration of corticosterone (500 micrograms.100 g body wt-1.day-1 sc) to intact or adrenalectomized rats, kept at 28 degrees C, produced a marked decrease of UCP mitochondrial content and cellular mRNA levels in a time-dependent manner (30% by 12 h and 50% by 24 h). Pretreatment of intact rats with corticosterone virtually abolished the UCP mRNA response to cold and norepinephrine (NE). In contrast, when rats had been preexposed to cold for 96 h, the injection of corticosterone did not affect UCP mRNA. These results show that corticosterone is a powerful inhibitor of UCP gene expression in vivo. Corticosterone inhibits both basal gene expression at thermoneutrality and the response to adrenergic stimulation either by cold or exogenous NE, suggesting a direct action on BAT. The data further suggest that corticosterone inhibits the initial accumulation of UCP mRNA mediated by UCP gene transcription, rather than accelerating the degradation of UCP mRNA.

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