scholarly journals Metformin Treatment Attenuates Brain Inflammation and Rescues Pacap/Vip Neuropeptide Alterations in Mice Fed a High-Fat Diet

2021 ◽  
Vol 22 (24) ◽  
pp. 13660
Author(s):  
Mawj Mandwie ◽  
Jocelyn Karunia ◽  
Aram Niaz ◽  
Kevin A. Keay ◽  
Giuseppe Musumeci ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Underlying Mechanism ◽  
Brain Regions ◽  
Brain Inflammation ◽  
Low Grade ◽  
Metformin Treatment ◽  
High Fat ◽  
Activation Markers ◽  
Beneficial Effects ◽  
Therapeutic Activities

High-fat diet (HFD)-induced comorbid cognitive and behavioural impairments are thought to be the result of persistent low-grade neuroinflammation. Metformin, a first-line medication for the treatment of type-2 diabetes, seems to ameliorate these comorbidities, but the underlying mechanism(s) are not clear. Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) are neuroprotective peptides endowed with anti-inflammatory properties. Alterations to the PACAP/VIP system could be pivotal during the development of HFD-induced neuroinflammation. To unveil the pathogenic mechanisms underlying HFD-induced neuroinflammation and assess metformin’s therapeutic activities, (1) we determined if HFD-induced proinflammatory activity was present in vulnerable brain regions associated with the development of comorbid behaviors, (2) investigated if the PACAP/VIP system is altered by HFD, and (3) assessed if metformin rescues such diet-induced neurochemical alterations. C57BL/6J male mice were divided into two groups to receive either standard chow (SC) or HFD for 16 weeks. A further HFD group received metformin (HFD + M) (300 mg/kg BW daily for 5 weeks) via oral gavage. Body weight, fasting glucose, and insulin levels were measured. After 16 weeks, the proinflammatory profile, glial activation markers, and changes within the PI3K/AKT intracellular pathway and the PACAP/VIP system were evaluated by real-time qPCR and/or Western blot in the hypothalamus, hippocampus, prefrontal cortex, and amygdala. Our data showed that HFD causes widespread low-grade neuroinflammation and gliosis, with regional-specific differences across brain regions. HFD also diminished phospho-AKT(Ser473) expression and caused significant disruptions to the PACAP/VIP system. Treatment with metformin attenuated these neuroinflammatory signatures and reversed PI3K/AKT and PACAP/VIP alterations caused by HFD. Altogether, our findings demonstrate that metformin treatment rescues HFD-induced neuroinflammation in vulnerable brain regions, most likely by a mechanism involving the reinstatement of PACAP/VIP system homeostasis. Data also suggests that the PI3K/AKT pathway, at least in part, mediates some of metformin’s beneficial effects.

scholarly journals 3,5 Diiodo-l-Thyronine (T2) Promotes the Browning of White Adipose Tissue in High-Fat Diet-Induced Overweight Male Rats Housed at Thermoneutrality

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 256 ◽  
Author(s):  
Rosalba Senese ◽  
Federica Cioffi ◽  
Rita De Matteis ◽  
Giuseppe Petito ◽  
Pieter de Lange ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fat Mass ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Underlying Mechanism ◽  
Male Rats ◽  
Standard Diet ◽  
High Fat ◽  
Beneficial Effects ◽  
Adipose Cells

The conversion of white adipose cells into beige adipose cells is known as browning, a process affecting energy metabolism. It has been shown that 3,5 diiodo-l-thyronine (T2), an endogenous metabolite of thyroid hormones, stimulates energy expenditure and a reduction in fat mass. In light of the above, the purpose of this study was to test whether in an animal model of fat accumulation, T2 has the potential to activate a browning process and to explore the underlying mechanism. Three groups of rats were used: (i) receiving a standard diet for 14 weeks; (ii) receiving a high-fat diet (HFD) for 14 weeks; and (iii) receiving a high fat diet for 10 weeks and being subsequently treated for four weeks with an HFD together with the administration of T2. We showed that T2 was able to induce a browning in the white adipose tissue of T2-treated rats. We also showed that some miRNA (miR133a and miR196a) and MAP kinase 6 were involved in this process. These results indicate that, among others, the browning may be another cellular/molecular mechanism by which T2 exerts its beneficial effects of contrast to overweight and of reduction of fat mass in rats subjected to HFD.

scholarly journals Comparative Evaluation of the Effect of Metformin and Insulin on Gut Microbiota and Metabolome Profiles of Type 2 Diabetic Rats Induced by the Combination of Streptozotocin and High-Fat Diet

2022 ◽  
Vol 12 ◽  
Author(s):  
Nan Hu ◽  
Qi Zhang ◽  
Hui Wang ◽  
Xuping Yang ◽  
Yan Jiang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Fat Diet ◽  
Insulin Treatment ◽  
Serum Levels ◽  
Underlying Mechanism ◽  
Diabetic Rats ◽  
Therapeutic Effects ◽  
Metformin Treatment ◽  
High Fat

Lately, an increasing number of studies have investigated the relationship between metformin and gut microbiota, suggesting that metformin exerts part of its hypoglycemic effect through the microbes. However, its underlying mechanism remains largely undetermined. In the present study, we investigated the effects of metformin on gut microbiota and metabolome profiles in serum and compared it with insulin treatment in rats with type 2 diabetes mellitus (T2DM). Diabetic rats (DM group) were induced by a combination of streptozotocin and high-fat diet (HFD). After 7 days, DM rats were treated with metformin (MET group) or insulin (INS group) for 3 weeks. The 16S rRNA sequencing of the gut microbiota and non-targeted metabolomics analysis of serum were conducted. A total of 13 bile acids (BAs) in serum were further determined and compared among different groups. The rat model of T2DM was well established with the typical diabetic symptoms, showing significantly increased blood glucose, AUC of OGTT, HOMA-IR, TC, TG, LDL-C and TBA. Metformin or insulin treatment could ameliorate symptoms of diabetes and partly recover the abnormal biochemical indicators. Compared with DM rats, the relative abundances of 13 genera were significantly changed after metformin treatment, while only three genera were changed after insulin treatment. The metformin and insulin treatments also exhibited different serum metabolome profiles in T2DM rats. Moreover, 64 differential metabolites were identified between MET and DM groups, whereas 206 were identified between INS and DM groups. Insulin treatment showed greater influence on amino acids, glycerophospholipids/glycerolipids, and acylcarnitine compared with the metformin treatment, while metformin had an important impact on BAs. Furthermore, metformin could significantly decrease the serum levels of CA, GCA, UDCA, and GUDCA, but increase the level of TLCA in DM rats. Insulin treatment significantly decreased the levels of CA, UDCA, and CDCA. Besides, several metabolites in serum or microbiota were positively or negatively correlated with some bacteria. Collectively, our findings indicated that metformin had a stronger effect on gut microbiota than insulin, while insulin treatment showed greater influence on serum metabolites, which provided novel insights into the therapeutic effects of metformin on diabetes.

The beneficial effects of Lactobacillus fermented black barley on high fat diet-induced fatty liver in rats

2021 ◽  
Author(s):  
Qi Guan ◽  
Xinwen Ding ◽  
Lingyue Zhong ◽  
Chuang Zhu ◽  
Pan Nie ◽  
...  
Keyword(s):  
Fatty Liver ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
High Fat ◽  
Beneficial Effects ◽  
Phytochemical Composition

Long term high-fat diet (HF) can cause metabolic disorders, which might induce fatty liver. Fermented whole cereal food exhibit healthy potential due to their unique phytochemical composition and probiotics. In...

scholarly journals A Standardized Extract Prepared from Red Orange and Lemon Wastes Blocks High-Fat Diet-Induced Hyperglycemia and Hyperlipidemia in Mice

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4291
Author(s):  
Santina Chiechio ◽  
Magda Zammataro ◽  
Massimo Barresi ◽  
Margherita Amenta ◽  
Gabriele Ballistreri ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Fat Diet ◽  
Extraction Process ◽  
Citrus Limon ◽  
High Fat ◽  
Beneficial Effects ◽  
Positive Effects ◽  
In Vivo Experiments ◽  
Glucose And Lipid Metabolism

Citrus fruits are a rich source of high-value bioactive compounds and their consumption has been associated with beneficial effects on human health. Red (blood) oranges (Citrus sinensis L. Osbeck) are particularly rich in anthocyanins (95% of which are represented by cyanidin-3-glucoside and cyanidin-3-6″-malonyl-glucoside), flavanones (hesperidin, narirutin, and didymin), and hydroxycinnamic acids (caffeic acid, coumaric acid, sinapic, and ferulic acid). Lemon fruit (Citrus limon) is also rich in flavanones (eriocitrin, hesperidin, and diosmin) and other polyphenols. All of these compounds are believed to play a very important role as dietary antioxidants due to their ability to scavenge free radicals. A standardized powder extract, red orange and lemon extract (RLE), was obtained by properly mixing anthocyanins and other polyphenols recovered from red orange processing waste with eriocitrin and other flavanones recovered from lemon peel by a patented extraction process. RLE was used for in vivo assays aimed at testing a potential beneficial effect on glucose and lipid metabolism. In vivo experiments performed on male CD1 mice fed with a high-fat diet showed that an 8-week treatment with RLE was able to induce a significant reduction in glucose, cholesterol and triglycerides levels in the blood, with positive effects on regulation of hyperglycemia and lipid metabolism, thus suggesting a potential use of this new phytoextract for nutraceutical purposes.

scholarly journals A 12-week low-carbohydrate, high-fat diet improves metabolic health outcomes over a control diet in a randomised controlled trial with overweight defence force personnel

2017 ◽  
Vol 42 (11) ◽  
pp. 1158-1164 ◽  
Author(s):  
Caryn Zinn ◽  
Julia McPhee ◽  
Nigel Harris ◽  
Micalla Williden ◽  
Kate Prendergast ◽  
...  
Keyword(s):  
Health Outcomes ◽  
High Fat Diet ◽  
Controlled Trial ◽  
Intervention Group ◽  
Density Lipoprotein ◽  
Metabolic Health ◽  
High Fat ◽  
Beneficial Effects ◽  
Low Carbohydrate ◽  
Randomised Controlled

Overweight, obesity, and poor health is becoming a global concern for defence force personnel. Conventional nutrition guidelines are being questioned for their efficacy in achieving optimal body composition and long-term health. This study compared the effects of a 12-week low-carbohydrate, high-fat diet with a conventional, high-carbohydrate, low-fat diet on weight reduction and metabolic health outcomes in at-risk New Zealand Defence Force personnel. In this randomised controlled trial, 41 overweight personnel were assigned to intervention and control groups. Weight, waist circumference, fasting lipids, and glycaemic control were assessed at baseline and at 12 weeks. Within-group change scores were analysed using the t statistic and interpreted using a p < 0.05 level of statistical significance. Between-group mean differences and confidence intervals were analysed using effect sizes and magnitude-based inferences. Twenty-six participants completed the trial (14 intervention, 12 control). Both groups showed statistically significant weight and waist circumference reductions; the intervention group significantly reduced triglycerides and serum glucose and significantly increased high-density lipoprotein cholesterol (HDLc). Relative to control, the intervention group showed small, possibly to likely beneficial effects for weight, triglycerides, glucose, insulin, and homeostasis model assessment of insulin resistance; moderate, likely beneficial effects for HDL cholesterol, triglyceride:HDLc ratio and HbA1c; and a small, likely harmful effect for low-density lipoprotein cholesterol. This dietary approach shows promise for short-term weight loss and improved metabolic health outcomes conditions compared with mainstream recommendations. It should be offered to defence force personnel at least as a viable alternative means to manage their weight and health.

The ameliorative effect of the Pyracantha fortuneana (Maxim.) H. L. Li extract on intestinal barrier dysfunction through modulating glycolipid digestion and gut microbiota in high fat diet-fed rats

2019 ◽  
Vol 10 (10) ◽  
pp. 6517-6532 ◽  
Author(s):  
Hang Xu ◽  
Chunfang Zhao ◽  
Yutian Li ◽  
Ruiyu Liu ◽  
Mingzhang Ao ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Fat Diet ◽  
Intestinal Barrier ◽  
High Fat ◽  
Barrier Dysfunction ◽  
Fruit Extract ◽  
Intestinal Barrier Dysfunction ◽  
Beneficial Effects ◽  
Obese Rats ◽  
Ameliorative Effect

Pyracantha fortuneana fruit extract (PFE) exhibits beneficial effects on IBF in association with the modulation of glycolipid digestion and gut microbiota in HFD-fed obese rats.

scholarly journals Beneficial effects of natural Jeju groundwaters on lipid metabolism in high-fat diet-induced hyperlipidemic rats

2014 ◽  
Vol 8 (2) ◽  
pp. 165 ◽  
Author(s):  
Yan-chao Wang ◽  
Jin-miao Lu ◽  
Hui-zi Jin ◽  
Ai-niu Ma ◽  
Jin-yang Zhang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Fat Diet ◽  
High Fat ◽  
Beneficial Effects

scholarly journals Anti-Obesity Effects of Combined Cornus officinalis and Ribes fasciculatum Extract in High-Fat Diet-Induced Obese Male Mice

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3187
Author(s):  
Eunkuk Park ◽  
Chang-Gun Lee ◽  
Hyoju Jeon ◽  
Hyesoo Jeong ◽  
Subin Yeo ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Insulin Action ◽  
Normal Diet ◽  
Male Mice ◽  
Impaired Glucose Metabolism ◽  
High Fat ◽  
Beneficial Effects ◽  
Cornus Officinalis ◽  
Treatment And Prevention ◽  
Obese Male

Medicinal plants are widely used as supplements for the treatment of various diseases because of their few side-effects. Here, we examined the anti-obesity effects of a mixture extract of Cornus officinalis and Ribes fasciculatum (CR) in high-fat diet (HFD)-induced obese male mice. Four week old male C57BL/6J mice were fed a normal diet (ND) or 60% high-fat diet (HFD) with different concentrations of CR extracts (75, 150, and 300 mg/kg/day) by oral administration for 12 weeks. CR extract administration prevented HFD-induced weight gain, hepatic steatosis, and adipocyte enlargement through the downregulation of adipogenesis-associated genes in obese male mice. In addition, CR administration improved the impaired glucose metabolism, insulin action, biochemical obesity parameters, and metabolic profiles in HFD-induced male mice. Consequently, the CR extract exhibited beneficial effects on HFD-induced systemic metabolic challenges. Taken together, our findings suggest that CR extract may be a potent therapeutic supplement for the treatment and prevention of obesity.

scholarly journals Hepatic Lipid Accumulation Induced by a High-fat Diet Is Regulated by Nrf2 Through Multiple Pathways

2021 ◽  
Author(s):  
sheng Qiu ◽  
Zerong Liang ◽  
Qinan Wu ◽  
Miao Wang ◽  
Mengliu Yang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Underlying Mechanism ◽  
Luciferase Assay ◽  
High Fat ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

Abstract BackgroundNuclear factor erythroid 2-related factor 2 (Nrf2) is reportedly involved in hepatic lipid metabolism, but the results are contradictory and the underlying mechanism thus remains unclear. Herein we focused on elucidating the effects of Nrf2 on hepatic adipogenesis and on determining the possible underlying mechanism. We established a metabolic associated fatty liver disease (MAFLD) model in high fat diet (HFD) fed Nrf2 knockout (Nrf2 KO) mice; further, a cell model of lipid accumulation was established using mouse primary hepatocytes (MPHs) treated with free fatty acids (FAs). Using these models, we investigated the relationship between Nrf2 and autophagy and its role in the development of MAFLD.ResultsWe observed that Nrf2 expression levels were up-regulated in patients with MAFLD and diet-induced obese mice. Nrf2 deficiency led to hepatic lipid accumulation in vivo and in vitro, in addition to, promoting lipogenesis mainly by increasing SREBP-1 activity. Moreover, Nrf2 deficiency attenuated autophagic flux and inhibited the fusion of autophagosomes and lysosomes in vivo and in vitro. Weakened autophagy caused reduced lipolysis in the liver. Importantly, Chromatin immunoprecipitation-qPCR (ChIP-qPCR) and dual-luciferase assay results proved that Nrf2 bound to LAMP1 promoter and regulated its transcriptional activity. We accordingly report that Nrf2-LAMP1 interaction has an indispensable role in Nrf2-regulated hepatosteatosis. ConclusionsThese data collectively confirm that Nrf2 deficiency promotes hepatosteatosis by enhancing SREBP-1 activity and attenuating autophagy. To conclude, our data reveal a novel multi-pathway effect of Nrf2 on lipid metabolism in the liver, and we believe that multi-target intervention of Nrf2 signaling is a promising new strategy for the prevention and treatment of MAFLD.

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