scholarly journals Mouse Microglial Calcitonin Receptor Knockout Impairs Hypothalamic Amylin Neuronal pSTAT3 Signaling but Lacks Major Metabolic Consequences

Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 51
Author(s):  
Bernd Coester ◽  
Thomas A. Lutz ◽  
Christelle Le Foll
Keyword(s):  
High Fat Diet ◽  
Energy Homeostasis ◽  
Arcuate Nucleus ◽  
Calcitonin Receptor ◽  
High Fat ◽  
Leptin Signaling ◽  
Physiological Relevance ◽  
Major Player ◽  
Significant Difference ◽  
Anorectic Effect

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.

scholarly journals Leptin Signaling Is Required for Leucine Deprivation-enhanced Energy Expenditure

2013 ◽  
Vol 289 (3) ◽  
pp. 1779-1787 ◽  
Author(s):  
Qian Zhang ◽  
Bin Liu ◽  
Ying Cheng ◽  
Qingshu Meng ◽  
Tingting Xia ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Normal Diet ◽  
Leptin Resistance ◽  
High Fat ◽  
Leptin Signaling ◽  
Fat Loss ◽  
Stimulation Of

Leptin signaling in the hypothalamus is crucial in energy homeostasis. We have previously shown that dietary deprivation of the essential amino acid leucine in mice stimulates fat loss by increasing energy expenditure. The involvement of leptin signaling in this regulation, however, has not been reported. Here, we show that leucine deprivation promotes leptin signaling in mice maintained on an otherwise normal diet and restores leptin responses in mice maintained on a high fat diet, a regimen known to induce leptin resistance. In addition, we found that leucine deprivation stimulated energy expenditure, and fat loss was largely blocked in db/db mice homozygous for a mutation in leptin receptor and a knock-in mouse line Y3F with abrogation of leptin receptor Tyr1138-mediated signal transducer and activator transcript 3 signaling. Overall, our studies describe a novel link between hypothalamic leptin signaling and stimulation of energy expenditure under leucine deprivation.

scholarly journals Postnatal administration of leptin antagonist mitigates susceptibility to obesity under high-fat diet in male αMUPA mice

2019 ◽  
Vol 317 (5) ◽  
pp. E783-E793
Author(s):  
Danielle Zecharia ◽  
Maayan Rauch ◽  
Adi Sharabi-Nov ◽  
Snait Tamir ◽  
Roee Gutman
Keyword(s):  
Body Weight ◽  
Energy Expenditure ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
Strain Differences ◽  
High Fat ◽  
Leptin Signaling ◽  
Diet Induced Obesity ◽  
Lower Body Weight ◽  
Type Plasminogen Activator

Perturbations in postnatal leptin signaling have been associated with altered susceptibility to diet-induced obesity (DIO) under high-fat-diet (HFD), albeit with contradicting evidence. Previous studies have shown that alpha murine urokinase-type plasminogen activator (αMUPA) mice have a higher and longer postnatal leptin surge compared with their wild types (WTs) as well as lower body weight and food intake under regular diet (RD). Here we explored αMUPA's propensity for DIO and the effect of attenuating postnatal leptin signaling with leptin antagonist (LA) on energy homeostasis under both RD and HFD. Four-day-old αMUPA pups were treated on alternate days until postnatal day 18 with either vehicle or LA (10 or 20 mg·day−1·kg−1) and weaned into RD or HFD. Compared with RD-fed αMUPA males, HFD-fed αMUPA males showed higher energy intake, even when corrected for body weight difference, and became hyperinsulinemic and obese. Additionally, HFD-fed αMUPA males gained body weight at a higher rate than their WTs mainly because of strain differences in energy expenditure. LA administration did not affect strain differences under RD but attenuated αMUPA’s hyperinsulinemia and DIO under HFD, most likely by mediating energy expenditure. Together with our previous findings, these results suggest that αMUPA’s leptin surge underlies its higher susceptibility to obesity under HFD, highlighting the role of leptin-related developmental processes in inducing obesity in a postweaning obesogenic environment, at least in αMUPA males. This study therefore supports the use of αMUPA mice for elucidating developmental mechanisms of obesity and the efficacy of early-life manipulations via leptin surge axis in attenuating DIO.

Pengaruh Pemberian Ekstrak Anggur Laut terhadap Penurunan Kadar Kolesterol LDL Rattus norvegicus Jantan yang Mendapat Diet Tinggi Lemak

2020 ◽  
Vol 17 (2) ◽  
pp. 192
Author(s):  
RONALDO LAU ◽  
SULISTIANA PRABOWO ◽  
RIAMI RIAMI
Keyword(s):  
Cholesterol Level ◽  
Rattus Norvegicus ◽  
High Fat Diet ◽  
Ldl Cholesterol ◽  
White Male ◽  
Standard Diet ◽  
High Fat ◽  
Caulerpa Racemosa ◽  
Significant Difference ◽  
Male Wistar Rats

<p align="justify"><strong>ABSTRACT</strong><strong></strong></p><p align="justify"><strong>Background</strong>: High fat diet increase the absorption of lipid in the intestinum, that can lead to increase LDL cholesterol level in the blood. Sea grapes extract (<em>Caulerpa racemosa</em>) contains antioxidant polyphenolic group that can reduce MTP and ACAT-2 in the body that can decrease LDL cholesterol level in the blood.The purpose of this study is to know the effect of sea grapes extract  on decreasing LDL cholesterol of white male Wistar rats (<em>Rattus norvegicus</em>) fed with high fat diet.</p><p align="justify"><strong>Method</strong>:  24 white male Wistar rats, that divided into 3 groups: 1) group of rats fed with standard diet for 28 days; 2) group of rats fed with high fat diet for 28 days; 3) group of rats fed with high fat diet for 28 days and given 10 gram/kg body weight/day of sea grapes extract on 15<sup>th</sup>-28<sup>th</sup> days. Then the blood LDL cholesterol level measured on the 29<sup>th</sup> day.</p><p align="justify"><strong>Result :</strong> One-Way ANOVA Test showed there was significant difference (p=0.004) of LDL level between the group of rats fed with standard diet (12.37 mg/dl) compared to group of rats fed with high fat diet (17.87 mg/dl). There was significant difference (p=0.001) of LDL level between the group of rats fed with high fat diet (17.87 mg/dl) compared to group of rats fed with high fat diet and sea grapes extract (10.12 mg/dl).</p><p align="justify"><strong>Conclusion: </strong>high fat diet significantly increase blood LDL cholesterol level and sea grapes extract (<em>Caulerpa racemosa</em>) significantly decrease blood LDL cholesterol level.</p><p align="justify"> </p><p align="justify"><strong>Keywords :</strong>Sea grapes extract, LDL cholesterol, high fat diet</p>

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.

Particular Matter of Motor Vehicle Exposure and High-Fat Diet Effects on Kidney Histopathology, Creatinine, and Malondialdehyde (MDA) Levels in Wistar Rats

2021 ◽  
Vol 5 (3) ◽  
pp. 124-128
Author(s):  
Rizka Veni ◽  
Awal Prasetyo ◽  
Muflihatul Muniroh
Keyword(s):  
High Fat Diet ◽  
Wistar Rats ◽  
Motor Vehicle ◽  
Histopathological Change ◽  
Normal Diet ◽  
Control Group ◽  
High Fat ◽  
Control Group Design ◽  
Treatment Groups ◽  
Significant Difference

This study aims to analyze the effect of combination of motor vehicle particular matter exposure and high-fat diet in kidney histopathology, creatinine levels, and MDA levels in Wistar rats. This study used a posttest-only control group design. Eighteen healthy male Wistar rats were divided into three groups. The intervention groups received motor vehicle fume exposure for 100 s with normal diet (X1) or high-fat diet (X2), and the control group received no exposure (C). Data analysis was processed with a SPSS 25.0 computer program by using the one-way ANOVA test followed by post hoc LSD. The degree of kidney histopathological damage showed significant differences between the X1 and X2 groups when compared with the control group (p < 0.05). The results of the creatinine level examination found a significant difference between the X2 and C groups (p < 0.05) and the treatment groups X1 and X2 (p < 0.05). The results of kidney MDA level examination showed a significant difference between the treatment groups (X1 and X2) and the control group (p < 0.05). The combination of particular matter of motor vehicle fumes exposure and high-fat diet could induce kidney damage through histopathological change and increased creatinine levels and kidney MDA levels in Wistar rats.

The impact of ageing, fasting and high-fat diet on central and peripheral glucose tolerance and glucose-sensing neural networks in the arcuate nucleus

2017 ◽  
Vol 29 (10) ◽  
pp. e12528 ◽  
Author(s):  
M. van den Top ◽  
F.-Y. Zhao ◽  
R. Viriyapong ◽  
N. J. Michael ◽  
A. C. Munder ◽  
...  
Keyword(s):  
Neural Networks ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Arcuate Nucleus ◽  
Glucose Sensing ◽  
High Fat ◽  
The Impact

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 COMPARISON EFFECT OF CV 12, ST 36 AND ST 40 EA ON SHORT TERM ENERGY BALANCE REGULATION IN HIGH FAT DIET RAT

2017 ◽  
Vol 52 (3) ◽  
pp. 174
Author(s):  
Purwo Sri Rejeki ◽  
Harjanto Harjanto ◽  
Raden Argarini ◽  
Imam Subadi
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Energy Balance ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
Continuous Wave ◽  
Positive Control ◽  
Control Group ◽  
High Fat ◽  
Short Term

The aim of this study was to determine the comparative effects of EA (EA) on the CV12, ST36 and ST40 to weight gain prevention over the short-term regulation of energy balance. The study was conducted with a completely randomized design. Rats were divided into five groups: negative control group (no treatment, n=5), positive control (sham EA/back, n=5), EA CV 12 (n=6), EA ST 36 (n=6) and EA ST 40 (n=7). Rats were exposed to high-fat diet for two weeks and EA was simultaneously performed once daily, five days a week for two weeks with 2 Hz, for 10 minutes with continuous wave. Body weight, BMI, front limb circumference and rear were measured during study. Levels of blood glucose, cholesterol, triglycerides, LDL and HDL were measured at the end of the study; which reflects the short-term regulation of energy homeostasis. For weight loss, EA CV12, ST36 and ST40 group have lost weight significantly compared to the negative and positive control group. The ST40 group has a significant decrease than ST36 and CV12. The most significant decrease in BMI found in the ST40 group. EA did not affect blood glucose levels, but modulated blood lipid profile. In ST 40 group there was a significant decrease in cholesterol, LDL and triglycerides. EA at point ST 40 is potential in preventing increased body weight and BMI in rats exposed to high-fat diet compared to the CV 12 and ST 36. ST 40 is a point with a potential of lowering LDL and triglycerides serum so that it can play a role in the short term regulation of energy homeostasis but also in the prevention of dyslipidemia.

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