High Fat Diet Mediates Amyloid-β Cleaving Enzyme 1 Phosphorylation and SUMOylation, Enhancing Cognitive Impairment in APP/PS1 Mice

2021 ◽  
pp. 1-14
Author(s):  
Jian Bao ◽  
Zheng Liang ◽  
Xiaokang Gong ◽  
Jing Yu ◽  
Yifan Xiao ◽  
...  
Keyword(s):  
Cognitive Performance ◽  
High Fat Diet ◽  
Amyloid Β ◽  
Normal Diet ◽  
Standard Diet ◽  
High Fat ◽  
Augmented Learning ◽  
Biochemical Analyses ◽  
Modifiable Lifestyle Factors

Background: Alzheimer’s disease (AD) is the most common form of dementia in older adults and extracellular accumulation of amyloid-β (Aβ) is one of the two characterized pathologies of AD. Obesity is significantly associated with AD developing factors. Several studies have reported that high fat diet (HFD) influenced Aβ accumulation and cognitive performance during AD pathology. However, the underlying neurobiological mechanisms have not yet been elucidated. Objective: The objective of this study was to explore the underlying neurobiological mechanisms of HFD influenced Aβ accumulation and cognitive performance during AD pathology. Methods: 2.5-month-old male APP/PS1 mice were randomly separated into two groups: 1) the normal diet (ND) group, fed a standard diet (10 kcal%fat); and 2) the HFD group, fed a high fat diet (40 kcal%fat, D12492; Research Diets). After 4 months of HFD or ND feeding, mice in the two groups were subjected for further ethological, morphological, and biochemical analyses. Results: A long-term HFD diet significantly increased perirenal fat and impaired dendritic integrity and aggravated neurodegeneration, and augmented learning and memory deficits in APP/PS1 mice. Furthermore, the HFD increased beta amyloid cleaving enzyme 1 (BACE1) dephosphorylation and SUMOylation, resulting in enhanced enzyme activity and stability, which exacerbated the deposition of amyloid plaques. Conclusion: Our study demonstrates that long-term HFD consumption aggravates amyloid-β accumulation and cognitive impairments, and that modifiable lifestyle factors, such as obesity, can induce BACE1 post-modifications which may contribute to AD pathogenesis.

Transgenic MSH overexpression attenuates the metabolic effects of a high-fat diet

2007 ◽  
Vol 293 (1) ◽  
pp. E121-E131 ◽  
Author(s):  
Michelle Lee ◽  
Andrea Kim ◽  
Streamson C. Chua ◽  
Silvana Obici ◽  
Sharon L. Wardlaw
Keyword(s):  
High Fat Diet ◽  
Metabolic Effects ◽  
High Fat ◽  
Fat Percentage ◽  
Male And Female ◽  
Fat Accumulation ◽  
Low Fat Diet ◽  
Hepatic Fat ◽  
Biochemical Analyses

To determine whether long-term melanocortinergic activation can attenuate the metabolic effects of a high fat diet, mice overexpressing an NH2-terminal POMC transgene that includes α- and γ3-MSH were studied on either a 10% low-fat diet (LFD) or 45% high-fat diet (HFD). Weight gain was modestly reduced in transgenic (Tg-MSH) male and female mice vs. wild type (WT) on HFD ( P < 0.05) but not LFD. Substantial reductions in body fat percentage were found in both male and female Tg-MSH mice on LFD ( P < 0.05) and were more pronounced on HFD ( P < 0.001). These changes occurred in the absence of significant feeding differences in most groups, consistent with effects of Tg-MSH on energy expenditure and partitioning. This is supported by indirect calorimetry studies demonstrating higher resting oxygen consumption and lower RQ in Tg-MSH mice on the HFD. Tg-MSH mice had lower fasting insulin levels and improved glucose tolerance on both diets. Histological and biochemical analyses revealed that hepatic fat accumulation was markedly reduced in Tg-MSH mice on the HFD. Tg-MSH also attenuated the increase in corticosterone induced by the HFD. Higher levels of Agrp mRNA, which might counteract effects of the transgene, were measured in Tg-MSH mice on LFD ( P = 0.02) but not HFD. These data show that long-term melanocortin activation reduces body weight, adiposity, and hepatic fat accumulation and improves glucose metabolism, particularly in the setting of diet-induced obesity. Our results suggest that long-term melanocortinergic activation could serve as a potential strategy for the treatment of obesity and its deleterious metabolic consequences.

Effects of a Long-Term High-Fat Diet and Switching from a High-Fat to Low-Fat, Standard Diet on Hepatic Fat Accumulation in Sprague-Dawley Rats

2008 ◽  
Vol 53 (12) ◽  
pp. 3206-3212 ◽  
Author(s):  
Katsuhisa Omagari ◽  
Shigeko Kato ◽  
Koichi Tsuneyama ◽  
Chisato Inohara ◽  
Yu Kuroda ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Standard Diet ◽  
Sprague Dawley ◽  
High Fat ◽  
Low Fat ◽  
Fat Accumulation ◽  
Sprague Dawley Rats ◽  
Hepatic Fat

scholarly journals Effect of concentrated Kurozu, a traditional Japanese vinegar, on expression of hepatic miR-34a, -149-3p, and -181a-5p in high-fat diet-fed mice

2020 ◽  
Vol 10 (1) ◽  
pp. 1
Author(s):  
Yoshihiko Shibayama
Keyword(s):  
Lipid Metabolism ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Standard Diet ◽  
High Fat ◽  
Expression Levels ◽  
Small Noncoding Rnas ◽  
Cell Functions ◽  
Micro Rnas

Background: Long-term high-fat diet (HFD) feeding, which can induce obesity, can also induce nonalcoholic steatohepatitis (NASH) and liver tumorigenesis. A previous study reported that concentrated Kurozu (CK) supplementation reduced the incidence of HFD-induced hepatic steatosis in mice. It was showed that CK supplementation improved dyslipidemia in animal and clinical study. Small noncoding RNAs, micro RNAs (miRs), play crucial roles in the biology of cell functions, lipid metabolism and neoplasms. However, the effect of CK treatment on the relationship between HFD and expression of miRs is unclear.Objective: To evaluate changes in the expression of hepatic miRs and lipid metabolism- associated genes on administering a HFD for 60 weeks in C57BL6J mice. The onset of hepatic steatosis induced by HFD treatment was also observed.Methods: The mice received a HFD, HFD with CK, or standard diet (SD) for 60 consecutive weeks. The effect of CK treatment on the expression levels of lipid metabolism-associated genes in the liver was evaluated.Results: HFD feeding significantly increased expression of Tnf, and significantly decreased Adipoq and Mlxipl in the liver. The ingestion of CK elevated the expression levels of Pgc-1α and Igfbp1 in the liver compared with the SD group. HFD feeding significantly increased the expression of miR-488-5p, and significantly decreased miR-29b and -122a-5p in the liver. The ingestion of CK elevated the expression levels of miR-34a, -149-3p, and -181a-5p in the liver compared with the SD group. Expression levels of miR-488-3p in the serum HFD group were significantly higher than in the SD group. The ingestion of CK elevated the expression levels of miR-181a-5p in the serum compared with the SD group.Conclusion: These results suggest that CK supplementation reduced the onset of hepatic hyperplasia, and increased hepatic miR-34a, -149-3p, and -181a-5p. These miRs may function as suppressors of tumors caused by HFD feeding.Key Words:  High-fat diet, carcinogenesis, Kurozu, microRNA, miR-34a, miR-122a-5p, miR-149, miR-181a, miR-488 

Central NMU signaling in body weight and energy balance regulation: evidence from NMUR2 deletion and chronic central NMU treatment in mice

2009 ◽  
Vol 297 (3) ◽  
pp. E708-E716 ◽  
Author(s):  
Emil Egecioglu ◽  
Karolina Ploj ◽  
Xiufeng Xu ◽  
Mikael Bjursell ◽  
Nicolas Salomé ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Balance ◽  
High Fat Diet ◽  
Body Weight Loss ◽  
Standard Diet ◽  
Wild Type ◽  
High Fat ◽  
Gene Encoding ◽  
Male And Female

To investigate the role of the central neuromedin U (NMU) signaling system in body weight and energy balance regulation, we examined the effects of long-term intracerebroventricular (icv) infusion of NMU in C57Bl/6 mice and in mice lacking the gene encoding NMU receptor 2. In diet-induced obese male and female C57BL/6 mice, icv infusion of NMU (8 μg·day−1·mouse−1) for 7 days decreased body weight and total energy intake compared with vehicle treatment. However, these parameters were unaffected by NMU treatment in lean male and female C57BL/6 mice fed a standard diet. In addition, female (but not male) NMUR2-null mice had increased body weight and body fat mass when fed a high-fat diet but lacked a clear body weight phenotype when fed a standard diet compared with wild-type littermates. Furthermore, female (but not male) NMUR2-null mice fed a high-fat diet were protected from central NMU-induced body weight loss compared with littermate wild-type mice. Thus, we provide the first evidence that long-term central NMU treatment reduces body weight, food intake, and adiposity and that central NMUR2 signaling is required for these effects in female but not male mice.

scholarly journals PO-178 Heat Treatment and Exercise Prevents Skeletal Muscle Insulin Resistance in Wistar Rats Fed High-Fat Diet

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Jiexiu Zhao ◽  
Fei Qin ◽  
Minxiao Xu ◽  
Yanan Dong ◽  
Zhongwei Wang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Protein Expression ◽  
High Fat Diet ◽  
Wistar Rats ◽  
Heat Exposure ◽  
Normal Diet ◽  
Brown Fat ◽  
Standard Diet ◽  
High Fat ◽  
Combined Exercise

Objective  Insulin resistance (IR) is associated with many related health complications. Previous studies demonstrate that heat and exercise independently reduce IR. The purpose of this study was to test the hypothesis that combined exercise and heating is even more favorable in reducing IR. Methods Male Wistar rats were randomly divided into five groups: exercise (NE; n=10), heated (HC; n=10), exercise and heated (HE; n=10), sedentary (NC; n=10), and normal diet plus sedentary (CC; n=10). All but the latter group was fed a high-fat diet (60% calories from fat) for 10 weeks while receiving heat and/or exercise exposure for latter 8 weeks. Following this regimen, protein expression from the soleus and extensor digitorum longus muscles, serum, and brown fat were analyzed using Western blotting. Results Exercise combined with heating shifted the metabolic characteristics of rats on a high-fat diet toward that observed in the rats on a standard diet. Specifically, eight weeks of combined heat and endurance exercise increased PGC-1α, CnA, CaMKIV and p38 MAPK protein expression in the soleus (P < 0.05), insulin protein expression in the serum (P < 0.05), and UCP1 protein expression in the brown fat (P < 0.05), when compared to the high fat fed sedentary group. There were some significant differences in responses (i.e., body weight and Leptin & Adiponectin concentrations) between the combined exercise and heat group relative to the exercise alone group. Conclusions  Exercise combined with heat exposure mitigates the development of IR, presumably from the Irisin pathway. The study provides potential non-pharmaceutical methods for therapeutic treatment of IR.

scholarly journals Impact of high-fat diet on lifespan, metabolism, fecundity and behavioral senescence in Drosophila

2020 ◽  
Author(s):  
Sifang Liao ◽  
Mirjam Amcoff ◽  
Dick R. Nässel
Keyword(s):  
Body Mass ◽  
High Fat Diet ◽  
Normal Diet ◽  
Long Term Effects ◽  
High Fat ◽  
Adipokinetic Hormone ◽  
Age Related ◽  
Lipid Stores ◽  
And Behavior

AbstractExcess consumption of high-fat diet (HFD) is likely to result in obesity and increases the predisposition to associated health disorders. Drosophila melanogaster has emerged as an important model to study the effects of HFD on metabolism, gut function, behavior, and ageing. In this study, we investigated the effects of HFD on physiology and behavior of female flies at different time-points over several weeks. We found that HFD decreases lifespan, and also with age leads to accelerated decline of climbing ability in both virgins and mated flies. In virgins HFD also increased sleep fragmentation with age. Furthermore, long-term exposure to HFD results in elevated adipokinetic hormone (AKH) transcript levels and an enlarged crop with increased lipid stores. We detected no long-term effects of HFD on body mass, or levels of triacylglycerides (TAG), glycogen or glucose, although fecundity was diminished. However, one week of HFD resulted in decreased body mass and elevated TAG levels in mated flies. Finally, we investigated the role of AKH in regulating effects of HFD during aging. Both with normal diet (ND) and HFD, Akh mutant flies displayed increased longevity compared to control flies. However, both mutants and controls showed shortened lifespan on HFD compared to ND. In flies exposed to ND, fecundity is decreased in Akh mutants compared to controls after one week, but increased after three weeks. However, HFD leads to a similar decrease in fecundity in both genotypes after both exposure times. Thus, long-term exposure to HFD increases AKH signaling, impairs lifespan and fecundity and augments age-related behavioral senescence.

scholarly journals Long-term inhibition of dipeptidyl peptidase IV improves glucose tolerance and preserves islet function in mice

2002 ◽  
pp. 717-727 ◽  
Author(s):  
MK Reimer ◽  
JJ Holst ◽  
B Ahren
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Dipeptidyl Peptidase ◽  
Normal Diet ◽  
Dipeptidyl Peptidase Iv ◽  
Islet Function ◽  
High Fat ◽  
Islet Size

OBJECTIVES: Inhibitors of the glucagon-like peptide-1 (GLP-1)-degrading enzyme, dipeptidyl peptidase IV (DPPIV), are being explored in the treatment of diabetes. We examined the long-term influence of a selective, orally active inhibitor of DPPIV (NVP DPP728), in normal female C57BL/6J mice and such mice rendered glucose-intolerant and insulin-resistant by feeding a high-fat diet. DESIGN: In mice fed a standard diet (11% fat) or a high-fat diet (58% fat), NVP DPP728 (0.12 micromol/g body weight) was administered in the drinking water for an 8 week period. RESULTS: DPPIV inhibition reduced plasma DPPIV activity to 0.01+/-0.03 mU/ml vs 3.26+/-0.19 mU/ml in controls (P<0.001). Glucose tolerance after gastric glucose gavage, as judged by the area under the curve for plasma glucose levels over the 120 min study period, was increased after 8 weeks by NVP DPP728 in mice fed normal diet (P=0.029) and in mice fed a high-fat diet (P=0.036). This was accompanied by increased plasma levels of insulin and intact GLP-1. Glucose-stimulated insulin secretion from islets isolated from NVP DPP728-treated animals after 8 weeks of treatment was increased as compared with islets from control animals at 5.6, 8.3 and 11.1 mmol/l glucose both in mice fed normal diet and in mice fed a high-fat diet (both P<0.05). Islet insulin and glucagon immunocytochemistry revealed that NVP DPP728 did not affect the islet architecture. However, the expression of immunoreactive glucose transporter isoform-2 (GLUT-2) was increased by DPPIV inhibition, and in mice fed a high-fat diet, islet size was reduced after treatment with NVP DPP728 from 16.7+/-2.6 x 10(3) microm(2) in controls to 7.6+/-1.0 x 10(3) microm(2) (P=0.0019). CONCLUSION: Long-term DPPIV inhibition improves glucose tolerance in both normal and glucose-intolerant mice through improved islet function as judged by increased GLUT-2 expression, increased insulin secretion and protection from increased islet size in insulin resistance.

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>

Formononetin Ameliorates Cognitive Disorder via PGC-1α Pathway in Neuroinflammation Conditions in High-Fat Diet-Induced Mice

2019 ◽  
Vol 18 (7) ◽  
pp. 566-577 ◽  
Author(s):  
Xinxin Fu ◽  
Tingting Qin ◽  
Jiayu Yu ◽  
Jie Jiao ◽  
Zhanqiang Ma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Fat Diet ◽  
Trifolium Pratense ◽  
Amyloid Β ◽  
Cognitive Disorder ◽  
Mechanism Study ◽  
High Fat ◽  
Neuroprotective Effects ◽  
Underlying Mechanisms

Background: Alzheimer’s disease is one of the most common neurodegenerative diseases in many modern societies. The core pathogenesis of Alzheimer’s disease includes the aggregation of hyperphosphorylated Tau and abnormal Amyloid-β generation. In addition, previous studies have shown that neuroinflammation is one of the pathogenesis of Alzheimer’s disease. Formononetin, an isoflavone compound extracted from Trifolium pratense L., has been found to have various properties including anti-obesity, anti-inflammation, and neuroprotective effects. But there are very few studies on the treatment of Alzheimer’s disease with Formononetin. Objective: The present study focused on the protective activities of Formononetin on a high-fat dietinduced cognitive decline and explored the underlying mechanisms. Methods: Mice were fed with HFD for 10 weeks and intragastric administrated daily with metformin (300 mg/kg) and Formononetin (20 and 40 mg/kg). Results: We found that Formononetin (20, 40 mg/kg) significantly attenuated the learning and memory deficits companied by weight improvement and decreased the levels of blood glucose, total cholesterol and triglyceride in high-fat diet-induced mice. Meanwhile, we observed high-fat diet significantly caused the Tau hyperphosphorylation in the hippocampus of mice, whereas Formononetin reversed this effect. Additionally, Formononetin markedly reduced the levels of inflammation cytokines IL-1β and TNF-α in high-fat diet-induced mice. The mechanism study showed that Formononetin suppressed the pro-inflammatory NF-κB signaling and enhanced the anti-inflammatory Nrf-2/HO-1 signaling, which might be related to the regulation of PGC-1α in the hippocampus of high-fat diet -induced mice. Conclusion: Taken together, our results showed that Formononetin could improve the cognitive function by inhibiting neuroinflammation, which is attributed to the regulation of PGC-1α pathway in HFD-induced mice.

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