scholarly journals Acupuncture Targeting SIRT1 in the Hypothalamic Arcuate Nucleus Can Improve Obesity in High-Fat-Diet-Induced Rats with Insulin Resistance via an Anorectic Effect

Obesity Facts ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 40-57 ◽  
Author(s):  
Qing Shu ◽  
Li Chen ◽  
Song Wu ◽  
Jia Li ◽  
Jianmin Liu ◽  
...  
Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 51
Author(s):  
Bernd Coester ◽  
Thomas A. Lutz ◽  
Christelle Le Foll

Amylin and leptin synergistically interact in the arcuate nucleus of the hypothalamus (ARC) to control energy homeostasis. Our previous rodent studies suggested that amylin-induced interleukin-6 release from hypothalamic microglia may modulate leptin signaling in agouti-related peptide expressing neurons. To confirm the physiological relevance of this finding, the calcitonin receptor (CTR) subunit of the amylin receptor was selectively depleted in microglia by crossing tamoxifen (Tx) inducible Cx3cr1-CreERT2 mice with CTR-floxed mice. Unexpectedly, male mice with CTR-depleted microglia (KO) gained the least amount of weight of all groups regardless of diet. However, after correcting for the tamoxifen effect, there was no significant difference for body weight, fat mass or lean mass between genotypes. No alteration in glucose tolerance or insulin release was detected. However, male KO mice had a reduced respiratory quotient suggesting a preference for fat as a fuel when fed a high fat diet. Importantly, amylin-induced pSTAT3 was decreased in the ARC of KO mice but this was not reflected in a reduced anorectic response. On the other hand, KO mice seemed to be less responsive to leptin’s anorectic effect while displaying similar ARC pSTAT3 as Tx-control mice. Together, these data suggest that microglial amylin signaling is not a major player in the control of energy homeostasis in mice.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ayumu Sugiura ◽  
Tatsuhiro Shimizu ◽  
Takeshi Kameyama ◽  
Tomohiko Maruo ◽  
Shin Kedashiro ◽  
...  

The hypothalamus plays a central role in homeostasis and aging. The hypothalamic arcuate nucleus (ARC) controls homeostasis of food intake and energy expenditure and retains adult neural stem cells (NSCs)/progenitor cells. Aging induces the loss of NSCs and the enhancement of inflammation, including the activation of glial cells in the ARC, but aging-associated alterations of the hypothalamic cells remain obscure. Here, we identified Sox2 and NeuN double-positive cells in a subpopulation of cells in the mouse ARC. These cells were reduced in number with aging, although NeuN-positive neuronal cells were unaltered in the total number. Diet-induced obesity mice fed with high-fat diet presented a similar hypothalamic alteration to aged mice. This study provides a new insight into aging-induced changes in the hypothalamus.


Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1598-1610 ◽  
Author(s):  
Maria M. Glavas ◽  
Melissa A. Kirigiti ◽  
Xiao Q. Xiao ◽  
Pablo J. Enriori ◽  
Sarah K. Fisher ◽  
...  

Childhood obesity increases the risk of adult obesity and diabetes, suggesting that early overnutrition permanently programs altered energy and glucose homeostasis. In the present studies, we used a mouse model to investigate whether early overnutrition increases susceptibility to obesity and insulin resistance in response to a high-fat diet (HFD). Litters from Swiss Webster dams were culled to three [chronic postnatal overnutrition (CPO)] or 10 (control) pups and then weaned onto standard chow at postnatal day (P) 23. At 6 wk of age, a subset of mice was placed on HFD, and glucose and insulin tolerance were examined at 16–17 wk of age. Leptin sensitivity was determined by hypothalamic phosphorylated signal transducer and activator of transcription-3 immunoreactivity at P16 and adulthood after ip leptin. CPO mice exhibited accelerated body weight gain and hyperleptinemia during the preweaning period but only a slightly heavier body weight and normal glucose tolerance in adulthood on standard chow diet. Importantly, CPO mice exhibited significant leptin resistance in the arcuate nucleus, demonstrated by reduced activation of phospho-signal transducer and activator of transcription-3, as early as P16 and throughout life, despite normalized leptin levels. In response to HFD, CPO but not control mice displayed insulin resistance in response to an insulin tolerance test. In conclusion, CPO mice exhibited early and persistent leptin resistance in the arcuate nucleus and, in response to HFD, rapid development of obesity and insulin resistance. These studies suggest that early overnutrition can permanently alter energy homeostasis and significantly increase susceptibility to obesity and insulin resistance.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Chang Yeon Kim ◽  
Jang Ho Ahn ◽  
Do Hyun Han ◽  
Cherl NamKoong ◽  
Hyung Jin Choi

The hypothalamus plays a central role in the integrated regulation of feeding and energy homeostasis. The hypothalamic arcuate nucleus (ARC) contains a population of neurons that express orexigenic and anorexigenic factors and is thought to control feeding behavior via several neuronal circuits. In this study, a comparative proteomic analysis of low-fat control diet- (LFD-) and high-fat diet- (HFD-) induced hypothalamic ARC was performed to identify differentially expressed proteins (DEPs) related to changes in body weight. In the ARC in the hypothalamus, 6621 proteins ( FDR < 0.01 ) were detected, and 178 proteins were categorized as DEPs (89 upregulated and 89 downregulated in the HFD group). Among the Gene Ontology molecular function terms associated with the DEPs, protein binding was the most significant. Fibroblast growth factor receptor substrate 2 (Frs2) and SHC adaptor protein 3 (Shc3) were related to protein binding and involved in the neurotrophin signaling pathway according to Kyoto Encyclopedia of Genes and Genomes analysis. Furthermore, high-precision quantitative proteomic analysis revealed that the protein profile of the ARC in mice with HFD-induced obesity differed from that in LFD mice, thereby offering insight into the molecular basis of feeding regulation and suggesting Frs2 and Shc3 as novel treatment targets for central anorexigenic signal induction.


2004 ◽  
Vol 286 (6) ◽  
pp. E1004-E1010 ◽  
Author(s):  
Dianne P. Figlewicz ◽  
Aryana Zavosh ◽  
Timothy Sexton ◽  
John F. Neumaier

The central nervous system (CNS) protein “tub” has been identified from the genetically obese “tubby” mouse. Although the native function of tub in situ is not understood, cell-based studies suggest that one of its roles may be as an intracellular signaling target for insulin. In normal animals, insulin acts at the hypothalamic arcuate nucleus (ARC) to regulate energy balance. Here we used a Herpes Simplex viral expression system to evaluate whether tub overexpression in the ARC of normal rats enhances this action of insulin. In chow-fed rats, tub overexpression had no effect on insulin action. In rats fed a high-fat diet snack in addition to chow, simulating the diet of Westernized societies, the body weight regulatory action of insulin was impaired, and tub overexpression further impaired insulin action. Thus an excess of tub at the ARC does not enhance the in vivo effectiveness of insulin and is not able to compensate for the “downstream” consequences of a high-fat diet to impair CNS body weight regulatory mechanisms.


Gene Therapy ◽  
2014 ◽  
Vol 21 (7) ◽  
pp. 638-644 ◽  
Author(s):  
V Vauthier ◽  
T D Swartz ◽  
P Chen ◽  
C Roujeau ◽  
M Pagnon ◽  
...  

2016 ◽  
Author(s):  
Ann-Kristin Picke ◽  
Lykke Sylow ◽  
Lisbeth L V Moller ◽  
Rasmus Kjobsted ◽  
Erik Richter ◽  
...  

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