scholarly journals POMC overexpression in the ventral tegmental area ameliorates dietary obesity

2011 ◽  
Vol 210 (2) ◽  
pp. 199-207 ◽  
Author(s):  
Lourdes M Andino ◽  
Daniel J Ryder ◽  
Alexandra Shapiro ◽  
Michael K Matheny ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Ventral Tegmental Area ◽  
Fluorescent Protein ◽  
Uncoupling Protein ◽  
Caloric Intake ◽  
Brown Norway ◽  
Brown Adipose ◽  
Ventral Tegmental ◽  
Green Fluorescent

The activation of proopiomelanocortin (POMC) neurons in different regions of the brain, including the arcuate nucleus of the hypothalamus (ARC) and the nucleus of the solitary tract curtails feeding and attenuates body weight. In this study, we compared the effects of delivery of a recombinant adeno-associated viral (rAAV) construct encoding POMC to the ARC with delivery to the ventral tegmental area (VTA). F344×Brown Norway rats were high-fat (HF) fed for 14 days after which self-complementary rAAV constructs expressing either green fluorescent protein or the POMC gene were injected using coordinates targeting either the VTA or the ARC. Corresponding increased POMC levels were found at the predicted injection sites and subsequent α-melanocyte-stimulating hormone levels were observed. Food intake and body weight were measured for 4 months. Although caloric intake was unaltered by POMC overexpression, weight gain was tempered with POMC overexpression in either the VTA or the ARC compared with controls. There were parallel decreases in adipose tissue reserves. In addition, levels of oxygen consumption and brown adipose tissue uncoupling protein 1 were significantly elevated with POMC treatment in the VTA. Interestingly, tyrosine hydroxylase levels were increased in both the ARC and VTA with POMC overexpression in either the ARC or the VTA. In conclusion, these data indicate a role for POMC overexpression within the VTA reward center to combat HF-induced obesity.

scholarly journals iBAT sympathetic innervation is not required for body weight loss induced by central leptin delivery

2018 ◽  
Vol 314 (3) ◽  
pp. E224-E231 ◽  
Author(s):  
Isabelle Côté ◽  
Yasemin Sakarya ◽  
Sara M. Green ◽  
Drake Morgan ◽  
Christy S. Carter ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Fluorescent Protein ◽  
Uncoupling Protein ◽  
Sympathetic Innervation ◽  
Body Weight Loss ◽  
Sham Operation ◽  
Long Term Study ◽  
Brown Adipose ◽  
Green Fluorescent

We evaluated the contribution of brown adipose tissue (BAT) sympathetic innervation on central leptin-mediated weight loss. In a short- and long-term study, F344BN rats were submitted to either a denervation of interscapular BAT (Denervated) or a sham operation (Sham). Animals from each group received the Ob (Leptin) or green fluorescent protein (GFP; Control) gene through a single injection of recombinant adeno-associated virus delivered centrally. Changes in body weight were recorded for 14 or 35 days, after which adipose tissues and skeletal muscles were weighed. In both studies, hypothalamic phosphorylated STAT3 (P-STAT3) was significantly higher in Sham-Leptin and Denervated-Leptin groups compared with their respective Control groups ( P < 0.01), indicating that leptin signaling was enhanced at the end point. We measured uncoupling protein 1 (UCP1), a marker of BAT thermogenic activity, and found a significant induction in Leptin in Sham animals ( P < 0.001) but not in Denervated animals, demonstrating that BAT UCP1 protein was only induced in Sham rats. Both Sham-Leptin and Denervated-Leptin rats lost ~15% of their initial body weight ( P < 0.001) by day 14 and reached a maximum of 18% body weight loss that stabilized over week 3 of treatment, indicating that sympathetic outflow to BAT is not required for leptin-mediated weight loss. In summary, interscapular BAT (iBAT) denervation did not prevent body weight loss following central leptin gene delivery. The present data show that sympathetic innervation of iBAT is not essential for leptin-induced body weight loss.

scholarly journals Neurons in ventral tegmental area tonically inhibit sympathetic outflow to brown adipose tissue: possible mediation of thermogenic signals from lateral habenula

2019 ◽  
Vol 316 (1) ◽  
pp. R6-R12 ◽  
Author(s):  
Mariana Brizuela ◽  
Steven J. Swoap ◽  
James Ang ◽  
William W. Blessing ◽  
Youichirou Ootsuka
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Ventral Tegmental Area ◽  
Dopamine Neurons ◽  
Lateral Habenula ◽  
Control Center ◽  
Brown Adipose ◽  
Medullary Raphe ◽  
Ventral Tegmental ◽  
Environmental Events

The lateral habenula (LHb), a nucleus involved in the response to salient, especially adverse, environmental events, is implicated in brown adipose tissue (BAT) thermogenesis caused by these events. LHb-elicited thermogenesis involves a neural pathway to the lower brain stem sympathetic control center in the medullary raphé. There are no direct connections from the LHb to the medullary raphé. LHb-mediated behavioral responses involve inhibitory control over the dopamine neurons in the ventral tegmental area (VTA), mediated via an excitatory drive from the LHb to GABAergic neurons in the tail of the VTA. We hypothesized that inhibition of the VTA is also involved in LHb-mediated BAT thermogenesis. To test this hypothesis, inhibition of neurons in the VTA with muscimol increased BAT sympathetic nerve discharge by 22.0 ± 9.2 dBμV ( n = 24, P < 0.0001) and BAT temperature by 1.2 ± 0.1°C ( P < 0.001). This response was abolished by inhibition of the medullary raphé neurons with muscimol. BAT thermogenesis initiated with focal injections of bicuculline in the LHb was reversed by subsequent blockade of GABAA receptors in the VTA with bicuculline. These results suggest that, at least in anesthetized rats, neurons in the VTA tonically inhibit BAT thermogenesis via a link, presently unknown, to the medullary raphé. Removal of this VTA-initiated inhibition is an important mechanism whereby LHb neurons activate BAT thermogenesis.

scholarly journals Corticotropin-Releasing Hormone-Mediated Pathway of Leptin to Regulate Feeding, Adiposity, and Uncoupling Protein Expression in Mice

Endocrinology ◽  
2003 ◽  
Vol 144 (8) ◽  
pp. 3547-3554 ◽  
Author(s):  
Takayuki Masaki ◽  
Go Yoshimichi ◽  
Seiichi Chiba ◽  
Tohru Yasuda ◽  
Hitoshi Noguchi ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
Mrna Expression ◽  
White Adipose Tissue ◽  
Energy Homeostasis ◽  
Uncoupling Protein ◽  
Hypothalamic Nucleus ◽  
Fat Cell ◽  
Brown Adipose

Abstract To examine the functional role of CRH in the regulation of energy homeostasis by leptin, we measured the effects of the CRH antagonist, α-helical CRH 8–41 (αCRH) on a number of factors affected by leptin activity. These included food intake, body weight, hypothalamic c-fos-like immunoreactivity (c-FLI), weight and histological characterization of white adipose tissue, and mRNA expressions of uncoupling protein (UCP) in brown adipose tissue (BAT) in C57Bl/6 mice. Central infusion of leptin into the lateral cerebroventricle (icv) caused significant induction of c-FLI in the paraventricular nucleus (PVN), ventromedial hypothalamic nucleus (VMH), dorsomedial hypothalamic nucleus, and arcuate nucleus. In all these nuclei, the effect of leptin on expression of cFLI in the PVN and VMH was decreased by treatment with αCRH. Administration of leptin markedly decreased cumulative food intake and body weight with this effect being attenuated by pretreatment with αCRH. In peripheral tissue, leptin up-regulated BAT UCP1 mRNA expression and reduced fat depositions in this tissue. Those changes in BAT were also decreased by treatment with αCRH. As a consequence of the effects on food intake or energy expenditure, treatment with αCRH attenuated the leptin-induced reduction of body adiposity, fat cell size, triglyceride contents, and ob mRNA expression in white adipose tissue. Taken together, these results indicate that CRH neurons in the PVN and VMH may be an important mediator for leptin that contribute to regulation of feeding, adiposity, and UCP expression.

Uncoupling protein 1 expression and high-fat diets

2011 ◽  
Vol 300 (1) ◽  
pp. R1-R8 ◽  
Author(s):  
Tobias Fromme ◽  
Martin Klingenspor
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Caloric Intake ◽  
High Fat ◽  
Uncoupling Protein 1 ◽  
Brown Adipocytes ◽  
Adaptive Thermogenesis ◽  
Brown Adipose ◽  
Thermoregulatory Function

Uncoupling protein 1 (Ucp1) is the key component of β-adrenergically controlled nonshivering thermogenesis in brown adipocytes. This process combusts stored and nutrient energy as heat. Cold exposure not only activates Ucp1-mediated thermogenesis to maintain normothermia but also results in adaptive thermogenesis, i.e., the recruitment of thermogenic capacity in brown adipose tissue. As a hallmark of adaptive thermogenesis, Ucp1 synthesis is increased proportionally to temperature and duration of exposure. Beyond this classical thermoregulatory function, it has been suggested that Ucp1-mediated thermogenesis can also be employed for metabolic thermogenesis to prevent the development of obesity. Accordingly, in times of excess caloric intake, one may expect a positive regulation of Ucp1. The general impression from an overview of the present literature is, indeed, an increased brown adipose tissue Ucp1 mRNA and protein content after feeding a high-fat diet (HFD) to mice and rats. The reported increases are very variable in magnitude, and the effect size seems to be independent of dietary fat content and duration of the feeding trial. In white adipose tissue depots Ucp1 mRNA is generally downregulated by HFD, indicating a decline in the number of interspersed brown adipocytes.

Regulation of the level of uncoupling protein in brown adipose tissue by insulin

1990 ◽  
Vol 258 (2) ◽  
pp. R418-R424 ◽  
Author(s):  
A. Geloen ◽  
P. Trayhurn
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Protein Content ◽  
White Adipose Tissue ◽  
Oxidase Activity ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Brown Adipose ◽  
Epididymal White Adipose Tissue

The role of insulin in the regulation of the thermogenic activity and capacity (uncoupling protein content) of brown adipose tissue (BAT) has been investigated using mice made diabetic with streptozotocin and then subsequently infused with different doses of insulin. After 12 days of diabetes, the animals received either 0, 8, 16, or 32 units of insulin.kg body wt-1.day-1 delivered by osmotic minipumps implanted subcutaneously for 12 days. After 12 days of diabetes, body weight, interscapular BAT, and epididymal white adipose tissue weights were each reduced. In BAT, significant decreases (P less than 0.05) in the mitochondrial protein content (63%), cytochrome oxidase activity (79%), mitochondrial GDP binding (51%), and the specific mitochondrial concentration and total tissue content of uncoupling protein (71 and 89%, respectively) were obtained, indicating that the thermogenic activity and capacity of the tissue were reduced in diabetes. The infusion of insulin at a dose of 8 units.kg-1.day-1 normalized mitochondrial GDP binding and doubled the concentration of uncoupling protein. Body weight, epididymal white adipose tissue weight, and the mitochondrial protein content of BAT were restored with 16 units of insulin.kg-1.day-1. Higher doses of insulin did not further increase the specific mitochondrial concentration of uncoupling protein, but the mitochondrial content (and thereby the total uncoupling protein content) of BAT was increased and blood glucose normalized. There was a significant correlation between the dose of insulin replacement and several of the parameters measured in BAT: mitochondrial protein content (r = 0.68, P less than 0.001), cytochrome oxidase activity (r = 0.54, P less than 0.001), and total uncoupling protein content (r = 0.68, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Chronic Hindbrain Administration of Oxytocin Elicits Weight Loss in Male Diet-Induced Obese Mice

2021 ◽  
Author(s):  
Melise Marie Edwards ◽  
Ha Khanh Nguyen ◽  
Adam Jay Herbertson ◽  
Andrew Dale Dodson ◽  
Tomasz Wietecha ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
Energy Intake ◽  
Uncoupling Protein ◽  
Post Injection ◽  
Reduced Body ◽  
Brown Adipose ◽  
Pre Treatment

Previous studies indicate that oxytocin (OT) administration reduces body weight in high fat diet (HFD)-induced obese (DIO) rodents through both reductions in food intake and increases in energy expenditure. We recently demonstrated that chronic hindbrain [fourth ventricular (4V)] infusions of OT evoke weight loss in DIO rats. Based on these findings, we hypothesized that chronic 4V OT would elicit weight loss in DIO mice. We assessed the effects of 4V infusions of OT (16 nmol/day) or vehicle over 28 days on body weight, food intake and body composition. OT reduced body weight by approximately 4.5±1.4% in DIO mice relative to OT pre-treatment body weight (P<0.05). These effects were associated with reduced adiposity and adipocyte size (inguinal white adipose tissue (IWAT)] (P<0.05) and attributed, in part, to reduced energy intake (P<0.05) at a dose that did not increase kaolin intake (P=NS). OT tended to increase uncoupling protein-1 expression in IWAT (0.05<P<0.1) suggesting that OT stimulates browning of WAT. To assess OT-elicited changes in brown adipose tissue (BAT) thermogenesis, we examined the effects of 4V OT on interscapular BAT temperature (TIBAT). 4V OT (1 μg) elevated TIBAT at 0.75 (P=0.08), 1, and 1.25 h (P<0.05) post-injection; a higher dose (5 μg) elevated TIBAT at 0.75, 1, 1.25, 1.5, 1.75 (P<0.05), and 2-h (0.05<P<0.1) post-injection. Together, these findings support the hypothesis that chronic hindbrain OT treatment evokes sustained weight loss in DIO mice by reducing energy intake and increasing BAT thermogenesis at a dose that is not associated with evidence of visceral illness.

Sex-related differences in energy balance in response to caloric restriction

2005 ◽  
Vol 289 (1) ◽  
pp. E15-E22 ◽  
Author(s):  
A. Valle ◽  
A. Català-Niell ◽  
B. Colom ◽  
F. J. García-Palmer ◽  
J. Oliver ◽  
...  
Keyword(s):  
Energy Efficiency ◽  
Adipose Tissue ◽  
Energy Balance ◽  
Caloric Restriction ◽  
Uncoupling Protein ◽  
Caloric Intake ◽  
Carbon Dioxide Production ◽  
Brown Adipose ◽  
Ad Libitum ◽  
Ad Libitum Intake

Sex-related differences in energy balance were studied in young Wistar rats fed standard chow pellets either ad libitum or in restricted amounts (60% of ad libitum intake) for 100 days. Caloric intake, indirect calorimetry, organ and adipose tissue weights, energy efficiency, liver mitochondrial respiration rate, and brown adipose tissue (BAT) uncoupling protein-1 (UCP1) content were measured. Ad libitum-fed females showed greater oxygen consumption (V̇o2) and carbon dioxide production (V̇co2) and lower energy efficiency than males. Caloric restriction induced a chronic drop of V̇o2 and V̇co2 in females but not in males over the period studied. Restricted females showed a better conservation of metabolic active organ mass and a greater decrease in adipose depots than restricted males. Moreover, changes of BAT size and UCP1 content suggest that BAT may be the main cause responsible for sex differences in the response of energy balance to caloric restriction. In conclusion, our results indicate that females under caloric restriction conditions deactivate facultative thermogenesis to a greater degree than males. This ability may have obvious advantages for female survival and therefore the survival of the species when food is limiting.

scholarly journals Cranberry Polyphenolic Extract Exhibits an Antiobesity Effect on High-Fat Diet–Fed Mice through Increased Thermogenesis

2020 ◽  
Vol 150 (8) ◽  
pp. 2131-2138 ◽  
Author(s):  
Fang Zhou ◽  
Jielong Guo ◽  
Xue Han ◽  
Yunxiao Gao ◽  
Qimin Chen ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
The Body ◽  
High Fat ◽  
Uncoupling Protein 1 ◽  
Polyphenolic Extract ◽  
Brown Adipose

ABSTRACT Background Although polyphenol-rich cranberry extracts reportedly have an antiobesity effect, the exact reason for this remains unclear. Objectives In light of the reported health benefits of the polyphenolic compounds in cranberry, we investigated the effects and mechanism of a cranberry polyphenolic extract (CPE) in high-fat diet (HFD)–fed obese mice. Methods The distributions of individual CPE compounds were characterized by HPLC fingerprinting. Male C57BL/6J mice (4 wk old) were fed for 16 wk normal diet (ND, 10% fat energy) or HFD (60% fat energy) with or without 0.75% CPE in drinking water (HFD + CPE). Body and adipose depot weights, indices of glucose metabolism, energy expenditure (EE), and expression of genes related to brown adipose tissue (BAT) thermogenesis, and inguinal/epididymal white adipose tissue (iWAT/eWAT) browning were measured. Results After 16 wk, the body weight was 22.5% lower in the CPE-treated mice than in the HFD group but remained 17.9% higher than in the ND group. CPE treatment significantly increased EE compared with that of the ND and HFD groups. The elevated EE was linked with BAT thermogenesis, and iWAT/eWAT browning, shown by the induction of thermogenic genes, especially uncoupling protein 1 (Ucp1), and browning-related genes, including Cd137, a member of the tumor necrosis factor receptor superfamily (Tnfrsf9). The mRNA expression and abundance of uncoupling protein 1 in BAT of CPE-fed mice were 5.78 and 1.47 times higher than in the HFD group, and 0.61 and 1.12 times higher than in the ND group, respectively. Cd137 gene expression in iWAT and eWAT of CPE-fed mice were 2.35 and 3.13 times higher than in the HFD group, and 0.84 and 1.39 times higher than in the ND group, respectively. Conclusions Dietary CPE reduced but did not normalize HFD-induced body weight gain in male C57BL/6J mice, possibly by affecting energy metabolism.

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