scholarly journals Central administration of resistin promotes short-term satiety in rats

2005 ◽  
Vol 153 (3) ◽  
pp. R1-R5 ◽  
Author(s):  
Sulay Tovar ◽  
Rubén Nogueiras ◽  
Loraine Y C Tung ◽  
Tamara R Castañeda ◽  
María Jesús Vázquez ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Food Intake ◽  
Energy Homeostasis ◽  
Therapeutic Potential ◽  
Central Administration ◽  
Fos Protein ◽  
Physiological Relevance ◽  
Affect Body Weight ◽  
Hypothalamic Structure ◽  
Fasted Rats

Objective: Several hormones expressed in white adipose tissue influence food intake at the central level. We sought to determine whether resistin, a circulating adipose-derived hormone in rodents, has actions on the hypothalamus by determining the effects of central resistin injection on food intake and on hypothalamic Fos protein expression. Design: As resistin expression in adipose tissue is influenced by altered nutritional status, we studied the effect of central resistin in both fed and pre-fasted rats. Results: In fasted rats, central injection of resistin decreased food intake acutely and increased the number of cells that express Fos protein in the arcuate nucleus but not in any other hypothalamic structure. The effect on food intake was dose-dependent and did not result in the formation of a conditioned taste aversion. Conclusions: Taken together, these results provide the first evidence documenting a central action of resistin, which could be involved in a feedback loop targeting the hypothalamus. On the other hand, since we observed resistin mRNA in the arcuate and ventromedial nuclei of the hypothalamus, it is also possible that brain-derived resistin serves as a neuropeptide involved in the regulation of energy homeostasis. However, since resistin-induced satiety was modest and transient, as central administration for several days did not affect body weight, the physiological relevance and therapeutic potential of the observed principal phenomenon may be limited.

scholarly journals Loss of Agouti-Related Peptide Does Not Significantly Impact the Phenotype of Murine POMC Deficiency

Endocrinology ◽  
2011 ◽  
Vol 152 (5) ◽  
pp. 1819-1828 ◽  
Author(s):  
Marcus P. Corander ◽  
Debra Rimmington ◽  
Benjamin G. Challis ◽  
Stephen O'Rahilly ◽  
Anthony P. Coll
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Central Administration ◽  
Melanocortin System ◽  
Double Knockout ◽  
Related Peptide ◽  
Agonist Action ◽  
Physiological Relevance ◽  
Brown Adipose

The hypothalamic melanocortin system is unique among neuropeptide systems controlling energy homeostasis, in that both anorexigenic proopiomelanocortin (POMC)-derived and orexigenic Agouti related-peptide (AgRP)-derived ligands act at the same receptors, namely melanocortin 3 and 4 receptors (MC3/4R). AgRP clearly acts as a competitive antagonist at MC3R and MC4R but may also have an inverse agonist action at these receptors. The physiological relevance of this remains uncertain. We generated a mouse lacking both POMC and AgRP [double knockout (DKO) mouse]. Phenotyping was performed in the absence and presence of glucocorticoids, and the response to central peptide administration was studied. The phenotype of DKO mice is indistinguishable from that of mice lacking Pomc alone, with both exhibiting highly similar degrees of hyperphagia and increased body length, fat, and lean mass compared with wild-type controls. After a 24-h fast, there was no difference in the refeeding response between Pomc−/− and DKO mice. Similarly, corticosterone supplementation caused an equivalent increase in food intake and body weight in both genotypes. Although the central administration of [Nle4, d-Phe7]-α-MSH to DKO mice caused a decrease in food intake and an increase in brown adipose tissue Ucp1 expression, both of which could be antagonized with the coadministration of AgRP, there was no effect of AgRP alone. These data suggest AgRP acts predominantly as a melanocortin antagonist. If AgRP has significant melanocortin-independent actions, these are of insufficient magnitude in vivo to impact any of the detailed phenotypes we have measured under a wide variety of conditions.

scholarly journals DsbA-L deficiency in T cells promotes diet-induced thermogenesis through suppressing IFN-γ production

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Haiyan Zhou ◽  
Xinyi Peng ◽  
Jie Hu ◽  
Liwen Wang ◽  
Hairong Luo ◽  
...  
Keyword(s):  
T Cells ◽  
Adipose Tissue ◽  
T Cell ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Whole Body ◽  
Brown Adipose ◽  
Ifn Γ ◽  
Diet Induced Thermogenesis

AbstractAdipose tissue-resident T cells have been recognized as a critical regulator of thermogenesis and energy expenditure, yet the underlying mechanisms remain unclear. Here, we show that high-fat diet (HFD) feeding greatly suppresses the expression of disulfide-bond A oxidoreductase-like protein (DsbA-L), a mitochondria-localized chaperone protein, in adipose-resident T cells, which correlates with reduced T cell mitochondrial function. T cell-specific knockout of DsbA-L enhances diet-induced thermogenesis in brown adipose tissue (BAT) and protects mice from HFD-induced obesity, hepatosteatosis, and insulin resistance. Mechanistically, DsbA-L deficiency in T cells reduces IFN-γ production and activates protein kinase A by reducing phosphodiesterase-4D expression, leading to increased BAT thermogenesis. Taken together, our study uncovers a mechanism by which T cells communicate with brown adipocytes to regulate BAT thermogenesis and whole-body energy homeostasis. Our findings highlight a therapeutic potential of targeting T cells for the treatment of over nutrition-induced obesity and its associated metabolic diseases.

scholarly journals Neonatal nutritional programming impairs adiponectin effects on energy homeostasis in adult life of male rats

2018 ◽  
Vol 315 (1) ◽  
pp. E29-E37 ◽  
Author(s):  
Mariana Peduti Halah ◽  
Paula Beatriz Marangon ◽  
Jose Antunes-Rodrigues ◽  
Lucila L. K. Elias
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Food Intake ◽  
White Adipose Tissue ◽  
Energy Homeostasis ◽  
Body Weight Gain ◽  
Adult Life ◽  
Male Rats ◽  
Nutritional Programming

Neonatal nutritional changes induce long-lasting effects on energy homeostasis. Adiponectin influences food intake and body weight. The aim of this study was to investigate the effects of neonatal nutritional programming on the central stimulation of adiponectin. Male Wistar rats were divided on postnatal (PN) day 3 in litters of 3 (small litter, SL), 10 (normal litter, NL), or 16 pups/dam (large litter, LL). We assessed body weight gain for 60 days, adiponectin concentration, and white adipose tissue weight. We examined the response of SL, NL, and LL rats on body weight gain, food intake, oxygen consumption (V̇o2), respiratory exchange ratio (RER), calorimetry, locomotor activity, phosphorylated-AMP-activated protein kinase (AMPK) expression in the hypothalamus, and uncoupling protein (UCP)-1 in the brown adipose tissue after central stimulus with adiponectin. After weaning, SL rats maintained higher body weight gain despite similar food intake compared with NL rats. LL rats showed lower body weight at weaning, with a catch up afterward and higher food intake. Both LL and SL groups had decreased plasma concentrations of adiponectin at PN60. SL rats had increased white adipose tissue. Central injection of adiponectin decreased body weight and food intake and increased V̇o2, RER, calorimetry, p-AMPK and UCP- 1 expression in NL rats, but it had no effect on SL and LL rats, compared with the respective vehicle groups. In conclusion, neonatal under- and overfeeding induced an increase in body weight gain in juvenile and early adult life. Unresponsiveness to central effects of adiponectin contributes to the imbalance of the energy homeostasis in adult life induced by neonatal nutritional programming.

scholarly journals Contribution of Neuroinflammation to the Pathogenesis of Cancer Cachexia

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Alessio Molfino ◽  
Gianfranco Gioia ◽  
Filippo Rossi Fanelli ◽  
Alessandro Laviano
Keyword(s):  
Adipose Tissue ◽  
Food Intake ◽  
Proinflammatory Cytokines ◽  
Adaptive Response ◽  
Energy Homeostasis ◽  
Cancer Cachexia ◽  
Behavioral Changes ◽  
Brain Areas ◽  
Functional Changes ◽  
The Brain

Inflammation characterizes the course of acute and chronic diseases and is largely responsible for the metabolic and behavioral changes occurring during the clinical journey of patients. Robust data indicate that, during cancer, functional modifications within brain areas regulating energy homeostasis contribute to the onset of anorexia, reduced food intake, and increased catabolism of muscle mass and adipose tissue. In particular, functional changes are associated with increased hypothalamic concentration of proinflammatory cytokines, which suggests that neuroinflammation may represent the adaptive response of the brain to peripheral challenges, including tumor growth. Within this conceptual framework, the vagus nerve appears to be involved in conveying alert signals to the hypothalamus, whereas hypothalamic serotonin appears to contribute to triggering catabolic signals.

scholarly journals Gqα/G11α deficiency in dorsomedial hypothalamus leads to obesity resulting from decreased energy expenditure and impaired sympathetic nerve activity

2020 ◽  
Author(s):  
Eric A. Wilson ◽  
Hui Sun ◽  
Zhenzhong Cui ◽  
Marshal T. Jahnke ◽  
Mritunjay Pandey ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Food Intake ◽  
Energy Expenditure ◽  
Energy Homeostasis ◽  
Dorsomedial Hypothalamus ◽  
Ambient Temperatures ◽  
Brown Adipose ◽  
Inhibit Food Intake ◽  
Specific Deletion

The G protein subunits Gqα and G11α (Gq/11α) couple receptors to phospholipase C, leading to increased intracellular calcium. In this study we investigated the consequences of Gq/11α deficiency in the dorsomedial hypothalamus (DMH), a critical site for the control of energy homeostasis. Mice with DMH-specific deletion of Gq/11α (DMHGq/11KO) were generated by stereotaxic injection of AAV-Cre-GFP into the DMH of Gqαflox/flox:G11α-/- mice. Compared to control mice that received DMH injection of AAV-GFP, DMHGq/11KO mice developed obesity associated with reduced energy expenditure without significant changes in food intake or physical activity. DMHGq/11KO mice showed no defects in the ability of the melanocortin agonist melanotan II to acutely stimulate energy expenditure or to inhibit food intake. At room temperature (22oC) DMHGq/11KO mice showed reduced sympathetic nervous system activity in brown adipose tissue (BAT) and heart, accompanied with decreased basal BAT Ucp1 gene expression and lower heart rates. These mice were cold intolerant when acutely exposed to cold (6oC for 5 hours) and had decreased cold-stimulated BAT Ucp1 gene expression. DMHGq/11KO mice also failed to adapt to gradually declining ambient temperatures and to develop adipocyte browning in inguinal white adipose tissue although their BAT Ucp1 was proportionally stimulated. Consistent with impaired cold-induced thermogenesis, the onset of obesity in DMHGq/11KO mice was significantly delayed when housed under thermoneutral conditions (30ºC). Thus, our results show that Gqα and G11α in the DMH are required for the control of energy homeostasis by stimulating energy expenditure and thermoregulation.

scholarly journals The Antiobesity Effects of Centrally Administered Neuromedin U and Neuromedin S Are Mediated Predominantly by the Neuromedin U Receptor 2 (NMUR2)

Endocrinology ◽  
2009 ◽  
Vol 150 (7) ◽  
pp. 3101-3109 ◽  
Author(s):  
Andrea Peier ◽  
Jennifer Kosinski ◽  
Kimberly Cox-York ◽  
Ying Qian ◽  
Kunal Desai ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Central Administration ◽  
Diet Induced Obesity ◽  
Inhibit Food Intake ◽  
Selective Agonists ◽  
Treatment Of Obesity ◽  
The Brain ◽  
Deficient Mice

Neuromedin U (NMU) and neuromedin S (NMS) are structurally related neuropeptides that have been reported to modulate energy homeostasis. Pharmacological data have shown that NMU and NMS inhibit food intake when administered centrally and that NMU increases energy expenditure. Additionally, NMU-deficient mice develop obesity, whereas transgenic mice overexpressing NMU are lean and hypophagic. Two high-affinity NMU/NMS receptors, NMUR1 and NMUR2, have been identified. NMUR1 is predominantly expressed in the periphery, whereas NMUR2 is predominantly expressed in the brain, suggesting that the effects of centrally administered NMU and NMS are mediated by NMUR2. To evaluate the role of NMUR2 in the regulation of energy homeostasis, we characterized NMUR2-deficient (Nmur2−/−) mice. Nmur2−/− mice exhibited a modest resistance to diet-induced obesity that was at least in part due to reduced food intake. Acute central administration of NMU and NMS reduced food intake in wild-type but not in Nmur2−/− mice. The effects on activity and core temperature induced by centrally administered NMU were also absent in Nmur2−/− mice. Moreover, chronic central administration of NMU and NMS evoked significant reductions in body weight and sustained reductions in food intake in mice. In contrast, Nmur2−/− mice were largely resistant to these effects. Collectively, these data demonstrate that the anorectic and weight-reducing actions of centrally administered NMU and NMS are mediated predominantly by NMUR2, suggesting that NMUR2-selective agonists may be useful for the treatment of obesity.

scholarly journals Thermogenic adipocytes: lineage, function and therapeutic potential

2020 ◽  
Vol 477 (11) ◽  
pp. 2071-2093 ◽  
Author(s):  
Alice E. Pollard ◽  
David Carling
Keyword(s):  
Adipose Tissue ◽  
Single Cell ◽  
Energy Homeostasis ◽  
Environmental Changes ◽  
Therapeutic Potential ◽  
Human Adipose Tissue ◽  
Lineage Tracing ◽  
Metabolic Demand ◽  
The Metabolic Syndrome ◽  
Metabolic Inflexibility

Metabolic inflexibility, defined as the inability to respond or adapt to metabolic demand, is now recognised as a driving factor behind many pathologies associated with obesity and the metabolic syndrome. Adipose tissue plays a pivotal role in the ability of an organism to sense, adapt to and counteract environmental changes. It provides a buffer in times of nutrient excess, a fuel reserve during starvation and the ability to resist cold-stress through non-shivering thermogenesis. Recent advances in single-cell RNA sequencing combined with lineage tracing, transcriptomic and proteomic analyses have identified novel adipocyte progenitors that give rise to specialised adipocytes with diverse functions, some of which have the potential to be exploited therapeutically. This review will highlight the common and distinct functions of well-known adipocyte populations with respect to their lineage and plasticity, as well as introducing the most recent members of the adipocyte family and their roles in whole organism energy homeostasis. Finally, this article will outline some of the more preliminary findings from large data sets generated by single-cell transcriptomics of mouse and human adipose tissue and their implications for the field, both for discovery and for therapy.

scholarly journals STAT3 but Not ERK2 Is a Crucial Mediator Against Diet-Induced Obesity via VMH Neurons

2021 ◽  
Author(s):  
Gabriel Henrique Marques Gonçalves ◽  
Sabrina Mara Tristão ◽  
Rafaella Eduarda Volpi ◽  
Gislaine Almeida-Pereira ◽  
Beatriz de Carvalho Borges ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Energy Homeostasis ◽  
Specific Pattern ◽  
Conditional Knockout ◽  
Steroidogenic Factor 1 ◽  
Diet Induced Obesity ◽  
Affect Body Weight

Leptin plays an important role in the protection against diet-induced obesity (DIO) by its actions in ventromedial hypothalamic (VMH) neurons. However, little is known about the intracellular mechanisms involved in these effects. To assess the role of the STAT3 and ERK2 signaling in neurons that express the steroidogenic factor 1 (SF1) in the VMH on energy homeostasis, we used cre-lox technology to generate male and female mice with specific disruption of STAT3 or ERK2 in SF1 neurons of the VMH. We demonstrated that the conditional knockout of STAT3 in SF1 neurons of the VMH did not affect body weight, food intake, energy expenditure and glucose homeostasis in animals on regular chow. However, when challenged with high-fat diet (HFD), loss of STAT3 in SF1 neurons caused a significant increase in body weight, food intake and energy efficiency that was more remarkable in females which also showed a decrease in energy expenditure. In contrast, deletion of ERK2 in SF1 neurons of VMH did not have any impact on energy homeostasis in both regular diet and HFD conditions. In conclusion, STAT3 but not ERK2 signaling in SF1 neurons of VMH plays a crucial role to protect against DIO in a sex-specific pattern.

Glucagon-like peptide 1-(7–36) amide acts at lateral and medial hypothalamic sites to suppress feeding in rats

2003 ◽  
Vol 284 (6) ◽  
pp. R1427-R1435 ◽  
Author(s):  
Rafael R. Schick ◽  
Jens P. Zimmermann ◽  
Thomas vorm Walde ◽  
Volker Schusdziarra
Keyword(s):  
Food Intake ◽  
Feeding Behavior ◽  
Effective Dose ◽  
Ventromedial Hypothalamus ◽  
Brain Regions ◽  
Central Administration ◽  
Minimal Effective Dose ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Fasted Rats

Glucagon-like peptide 1-(7–36) amide (GLP-1) potently inhibits rat feeding behavior after central administration. Because third ventricular injection of GLP-1 appeared to be less effective than lateral ventricular injection, we have reexamined this issue. In addition, we attempted to identify brain regions other than the paraventricular nucleus of the hypothalamus that are sensitive toward GLP-1-induced feeding suppression. Finally, we examined the local role of endogenous GLP-1 by specific GLP-1 receptor blockade. After lateral ventricular injection, GLP-1 significantly inhibited food intake of 24-h-fasted rats in a dose-dependent fashion with a minimal effective dose of 1 μg. After third ventricular injection, GLP-1 (1 μg) was similarly effective in suppressing food intake, which extends previous findings. Intracerebral microinjections of GLP-1 significantly suppressed food intake in the lateral (LH), dorsomedial (DMH), and ventromedial hypothalamus (VMH), but not in the medial nucleus of the amygdala. The minimal effective dose of GLP-1 was 0.3 μg at LH sites and 1 μg at DMH or VMH sites. LH microinjections of exendin-(9–39) amide, a GLP-1 receptor antagonist, at 1 or 2.5 μg did not alter feeding behavior in 24-h-fasted rats. In satiated animals, however, a single LH injection of 1 μg exendin-(9–39) amide significantly augmented food intake, but only during the first 20 min (0.6 vs. 0.1 g). With three repeated injections of 2.5 μg exendin-(9–39) amide every 20 min, 1-h food intake was significantly increased by 300%. These data strongly support and extend the concept of GLP-1 as a physiological regulator of food intake in the hypothalamus.

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.

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