scholarly journals Proteome Analysis of the Hypothalamic Arcuate Nucleus in Chronic High-Fat Diet-Induced Obesity

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Chang Yeon Kim ◽  
Jang Ho Ahn ◽  
Do Hyun Han ◽  
Cherl NamKoong ◽  
Hyung Jin Choi
Keyword(s):  
Protein Binding ◽  
Proteomic Analysis ◽  
High Fat Diet ◽  
Arcuate Nucleus ◽  
Control Diet ◽  
Protein Profile ◽  
Adaptor Protein ◽  
High Fat ◽  
Feeding Regulation ◽  
Hypothalamic Arcuate Nucleus

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.

Abstract 58: Angiotensin-(1-7) Mas Receptors In The Arcuate Nucleus Of The Hypothalamus Protect Against High Fat Diet-induced Insulin Resistance In Female Mice

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Darren Mehay ◽  
Sarah Bingaman ◽  
Yuval Silberman ◽  
Amy Arnold
Keyword(s):  
Body Composition ◽  
Insulin Sensitivity ◽  
Energy Balance ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Metabolic Regulation ◽  
Arcuate Nucleus ◽  
Control Diet ◽  
High Fat ◽  
Metabolic Outcomes

Angiotensin (Ang)-(1-7) is a protective hormone of the renin-angiotensin system that improves insulin sensitivity, glucose tolerance, and energy balance in obese rodents. Our recent findings suggest that Ang-(1-7) activates mas receptors (MasR) in the arcuate nucleus of the hypothalamus (ARC), a brain region critical to control of energy balance and glucose homeostasis, to induce these positive metabolic effects. The distribution of MasR in the ARC and their role in metabolic regulation, however, is unknown. We hypothesized: (1) MasR are expressed in the ARC; and (2) deletion of ARC MasR leads to worsened metabolic outcomes following high fat diet (HFD). To test this, male and female C57Bl/6J mice were fed a 60% HFD or matched control diet ad libitum for 12 weeks. RNAscope in situ hybridization was performed on coronal ARC sections in rostral-middle-caudal regions to determine percentage of MasR positive neurons (n=5/group). In a second experiment, we assessed body composition and insulin and glucose tolerance in transgenic mice with deletion of MasR in ARC neurons (MasR-flox with AAV5-hsyn-GFP-Cre). RNAscope revealed a wide distribution on MasR-positive cells throughout the rostral to caudal extent of the ARC. The average percentage of MasR positive neurons was increased in females versus males, with HFD tending to increase MasR expression in both sexes (control diet male: 11±2; control diet female: 17±3; HFD male: 15±5; HFD female: 24±2; p sex : 0.030; p diet : 0.066; p int : 0.615; two-way ANOVA). Deletion of MasR in ARC neurons worsened insulin sensitivity in HFD but not control diet females (area under the curve for change in glucose from baseline: -1989±1359 HFD control virus vs. 2530±1762 HFD Cre virus; p=0.016), while fasting glucose, glucose tolerance, and body composition did not change. There was no effect of ARC MasR deletion on metabolic outcomes in control diet or HFD male mice. These findings suggest females have more MasR positive neurons in the ARC compared to males, which may be a sex-specific protective mechanism for glucose homeostasis. While further studies are needed to explore the role of ARC MasR in metabolic regulation, these findings support targeting Ang-(1-7) as an innovative strategy in obesity.

scholarly journals Identification of Sox2 and NeuN Double-Positive Cells in the Mouse Hypothalamic Arcuate Nucleus and Their Reduction in Number With Aging

2021 ◽  
Vol 12 ◽  
Author(s):  
Ayumu Sugiura ◽  
Tatsuhiro Shimizu ◽  
Takeshi Kameyama ◽  
Tomohiko Maruo ◽  
Shin Kedashiro ◽  
...  
Keyword(s):  
Stem Cells ◽  
High Fat Diet ◽  
Arcuate Nucleus ◽  
High Fat ◽  
Double Positive ◽  
Diet Induced Obesity ◽  
Hypothalamic Arcuate Nucleus ◽  
Hypothalamic Cells ◽  
Induced Changes ◽  
Insight Into

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.

scholarly journals High-fat diet feeding reduces the expression of Rab3a, Rab3gap1, and Rab3Gap2 genes that are pivotal to neuronal exocytosis

2021 ◽  
Author(s):  
Luana Assis Ferreira ◽  
Fernando Victor Martins Rubatino ◽  
Mariana Lacerda de Freitas ◽  
Leonardo Rossi de Oliveira ◽  
Célio Jose de Castro Junior ◽  
...  
Keyword(s):  
Data Analysis ◽  
High Fat Diet ◽  
Arcuate Nucleus ◽  
Control Diet ◽  
Receptor Recycling ◽  
High Fat ◽  
Transcript Levels ◽  
General Network ◽  
Obesity Phenotype ◽  
Plasma Leptin

AbstractThe Rab3A and Rab3gaps are essential to the Ca+2-dependent neuronal exocytosis in the hypothalamus. The arcuate nucleus of the hypothalamus (ARC) controls food intake and energy expenditure. We have earlier described that the high-fat diet (HFD) feeding induces an obesity phenotype with high leptin production and alteration of proteins related to endosome sorting, and ubiquitination in the ARC of mice. In this study, real-time PCR data analysis revealed that HFD feeding decreases significantly Rab3a, Rab3gap1, and Rab3gap2 transcript levels in the ARC when compared to the group receiving a control diet. The decrease of Rab3gap1/2 transcript levels in the ARC was strongly associated with an increase in plasma leptin. Altogether, our studies demonstrate that HFD feeding could be altering the general network of endosome compartmentalization in the ARC of mice, contributing to a failure in exocytosis and receptor recycling.Graphical abstract

Catabolic action of insulin in rat arcuate nucleus is not enhanced by exogenous “tub” expression

2004 ◽  
Vol 286 (6) ◽  
pp. E1004-E1010 ◽  
Author(s):  
Dianne P. Figlewicz ◽  
Aryana Zavosh ◽  
Timothy Sexton ◽  
John F. Neumaier
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Intracellular Signaling ◽  
Insulin Action ◽  
Arcuate Nucleus ◽  
Expression System ◽  
The Body ◽  
High Fat ◽  
Hypothalamic Arcuate Nucleus

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.

scholarly journals Endospanin 1 silencing in the hypothalamic arcuate nucleus contributes to sustained weight loss of high fat diet obese mice

Gene Therapy ◽  
2014 ◽  
Vol 21 (7) ◽  
pp. 638-644 ◽  
Author(s):  
V Vauthier ◽  
T D Swartz ◽  
P Chen ◽  
C Roujeau ◽  
M Pagnon ◽  
...  
Keyword(s):  
Weight Loss ◽  
High Fat Diet ◽  
Arcuate Nucleus ◽  
Obese Mice ◽  
High Fat ◽  
Sustained Weight Loss ◽  
Hypothalamic Arcuate Nucleus

Proteomic analysis of the anti-obesity effect of Taeumjowui-Tang in high fat diet-induced obese mice

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
E Changkyun Park ◽  
SY Lee ◽  
SH Yun ◽  
WY Kim ◽  
Y Yi ◽  
...  
Keyword(s):  
Proteomic Analysis ◽  
High Fat Diet ◽  
Obese Mice ◽  
High Fat

scholarly journals Methionine restriction plus overload improves skeletal muscle and metabolic health in old mice on a high fat diet

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anandini Swaminathan ◽  
Andrej Fokin ◽  
Tomas Venckūnas ◽  
Hans Degens
Keyword(s):  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Muscle Mass ◽  
Body Mass ◽  
High Fat Diet ◽  
Control Diet ◽  
Metabolic Health ◽  
High Fat ◽  
Methionine Restriction ◽  
Old Mice

AbstractMethionine restriction (MR) has been shown to reduce the age-induced inflammation. We examined the effect of MR (0.17% methionine, 10% kCal fat) and MR + high fat diet (HFD) (0.17% methionine, 45% kCal fat) on body mass, food intake, glucose tolerance, resting energy expenditure, hind limb muscle mass, denervation-induced atrophy and overload-induced hypertrophy in young and old mice. In old mice, MR and MR + HFD induced a decrease in body mass. Muscle mass per body mass was lower in old compared to young mice. MR restored some of the HFD-induced reduction in muscle oxidative capacity. The denervation-induced atrophy of the m. gastrocnemius was larger in animals on MR than on a control diet, irrespective of age. Old mice on MR had larger hypertrophy of m. plantaris. Irrespective of age, MR and MR + HFD had better glucose tolerance compared to the other groups. Young and old mice on MR + HFD had a higher resting VO2 per body mass than HFD group. Mice on MR and MR + HFD had a resting respiratory quotient closer to 0.70, irrespective of age, indicating an increased utilization of lipids. In conclusion, MR in combination with resistance training may improve skeletal muscle and metabolic health in old age even in the face of obesity.

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