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Subject: search.filters.subject.High Fat Diet (HFD)

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    Co-supplementation of isomalto-oligosaccharides potentiates metabolic health benefits of polyphenol-rich cranberry extract in high fat diet-fed mice via enhanced gut butyrate production
    (Springer, 2017-11) Khare, Pragyanshu
    Cranberries are a rich source of polyphenolic antioxidants. Purified sugars or artificial sweeteners are being added to cranberry-based food products to mask tartness. Refined sugar and artificial sweeteners intake modulate gut microbiota and result in metabolic complications. We evaluated effects of isomalto-oligosaccharides (IMOs; sweet tasting non-digestible oligosaccharides) with cranberry extract (CRX) on high fat diet (HFD)-induced metabolic alterations in mice.
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    Isomalto-oligosaccharides, a prebiotic, functionally augment green tea effects against high fat diet-induced metabolic alterations via preventing gut dysbacteriosis in mic
    (Elsevier, 2017-09) Khare, Pragyanshu
    High fat diet (HFD)-induced alterations in gut microbiota and resultant ‘leaky gut’ phenomenon promotes metabolic endotoxemia, ectopic fat deposition, and low-grade systemic inflammation. Here we evaluated the effects of a combination of green tea extract (GTE) with isomalto-oligosaccharide (IMOs) on HFD-induced alterations in mice. Male Swiss albino mice were fed with HFD (58% fat kcal) for 12 weeks. Systemic adiposity, gut derangement parameters and V3-V4 region based 16S rRNA metagenomic sequencing, ectopic fat deposition, liver metabolome analysis, systemic and tissue inflammation, and energy homeostasis markers along with gene expression analysis in multiple tissues were done in mice supplemented with GTE, IMOs or their combination. The combination of GTE and IMOs effectively prevented HFD-induced adiposity and lipid accumulation in liver and muscle while normalizing fasting blood glucose, insulin, glucagon, and leptin levels. Co-administration of GTE with IMOs effectively modulated liver metabolome associated with lipid metabolism. It also prevented leaky gut phenotype and HFD-induced increase in circulating lipopolysaccharides and pro-inflammatory cytokines (e.g. resistin, TNF-α, and IL-1β) and reduction in anti-inflammatory cytokines (e.g. adiponectin and IL-6). Gene expression analysis across multiple tissues further supported these functional outcomes. Most importantly, this combination improved beneficial gut microbiota (Lactobacillus sp., Bifidobacteria, Akkermansia muciniphila, Roseburia spp.) abundances, restored Firmicutes/Bacteriodetes and improved Prevotella/Bacteroides proportions. In particular, a combination of these two agents has shown improved beneficial effects on multiple parameters studied. Data presented herein suggests that strategically chosen food components might be highly effective in the prevention of HFD-induced alterations and may further be developed as functional foods.
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    Coadministration of isomalto-oligosaccharides augments metabolic health benefits of cinnamaldehyde in high fat diet fed mice
    (Wiley, 2017-08) Khare, Pragyanshu
    Bacteriostatic properties of a potential anti-obesity agent cinnamaldehyde (CMN) may present untoward effects on the resident gut microbiota. Here, we evaluated whether the combination of Isomalto-oligosaccharides (IMOs) with CMN prevents unwanted effects of CMN on gut microbiota and associated metabolic outcomes in HFD-fed mice. Male Swiss albino mice divided into four groups (n = 10), were fed on normal chow, or HFD (58% fat kcal), HFD + CMN (10 mg kg−1) and HFD + CMN (10 mg kg−1) + IMOs (1 g kg−1) for 12 weeks. Effects on HFD-induced biochemical, histological, inflammatory and genomic changes in the gastrointestinal tract, liver, and visceral white adipose tissue were studied. Cosupplementation of CMN with IMOs potentiates its preventive action against HFD-induced increase in serum LPS and abundances of selected LPS producing bacteria (Enterobacteriaceae, Escherichia Coli, Cronobacter sp, Citrobacter sp., Klebsiella sp., Salmonella sp.). CMN and IMOs co-administration prevented HFD-induced decrease in selected beneficial gut bacterial abundances (Bifidobacteria, Roseburia sp., Akkermansia muciniphila, Feacalibacterium sp.). CMN's effects against HFD-induced increase in gut permeability, histological and inflammatory changes in the colon were further augmented by cosupplementation of IMOs. Similar effects were observed in hepatic inflammatory markers. Cosupplementation of CMN with IMOs and CMN alone administration prevented HFD-induced changes in peripheral hormones and lipid metabolism-related parameters. This study provides evidence that coadministration of IMOs with CMN potentiates its anti-obesity effect and limits the side effects of CMN on gastrointestinal flora. Further, this study gives us important direction for the development of a concept-based novel class of functional foods/nutraceuticals for improved metabolic health.
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    Protective effects of phyllanthin, a lignan from Phyllanthus amarus, against progression of high fat diet induced metabolic disturbances in mice
    (RSC, 2016) Khare, Pragyanshu
    Evidence based studies have proved the efficacy of plant derived bioactives against lifestyle oriented disorders as they can be incorporated in to the diet or diet based supplements. Phyllanthin is one such lignan from Phyllanthus amarus as well as different Phyllanthus species. Phyllanthin was evaluated as a chronic intervention (12 weeks) in mice, at a daily dose of 2 and 4 mg kg−1 of body weight along with a lard based high fat diet (HFD). Phyllanthin protected against HFD induced weight gain and adiposity. Phyllanthin supplementation reduced mRNA expression of adipogenic genes and increased expression of lipolytic genes in white adipose tissue. Treatment also showed reduction in liver triglyceride accumulation. HFD induced serum lipid disturbances were found to be restored by phyllanthin. Treatment reduced serum triglycerides and free fatty acids in HFD fed mice. Phyllanthin counteracted coexisting low grade inflammation and oxidative stress in adipose tissue and liver. Along with serum proinflammatory cytokines, expression of NF-κB and F4/80 was decreased by phyllanthin. Supplementation of phyllanthin accelerated glucose clearance along with alleviation of insulin resistance in terms of HOMA-IR. Furthermore, mRNA expression of the insulin receptor and insulin receptor substrate-1 was elevated by phyllanthin in liver and adipose tissue. The present study confirmed the protective effects of phyllanthin against HFD induced metabolic changes. Daily consumption of phyllanthin in the diet as a nutraceutical can ameliorate the development of metabolic disorders.
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    Dihydrocapsiate supplementation prevented high-fat diet–induced adiposity, hepatic steatosis, glucose intolerance, and gut morphological alterations in mice
    (Elsevier, 2018-03) Khare, Pragyanshu
    Despite the lipolytic and thermogenic properties of capsaicin, its putative use as a weight-lowering dietary supplement has been limited because of the burning sensation caused by capsaicin when it comes in contact with mucous membranes. A potential alternative to capsaicin are the capsinoids, nonpungent capsaicin analogs that exhibit effects similar to capsaicin. Whereas the antiobesity properties of capsinoids have been reported, the effectiveness of FDA-approved synthetic dihydrocapsiate has not yet been investigated. In the present study, we hypothesized that dihydrocapsiate might ameliorate high-fat diet (HFD)–induced metabolic disorders in a manner similar to capsaicin and therefore can be its nonpungent alternative. To test this hypothesis, HFD-fed mice were orally administered dihydrocapsiate (2 and 10 mg/kg body weight) for 12 weeks. Dihydrocapsiate modestly reduced the HFD-induced weight gain and significantly prevented the associated hyperglyceridemia and hyperinsulinemia while improving glucose tolerance. Histological and gene expression analysis showed that dihydrocapsiate significantly prevented the lipid accumulation in white adipose tissue and brown adipose tissue via targeting genes involved in energy expenditure and mitochondrial biogenesis, respectively. Dihydrocapsiate corrected hepatic triglyceride concentrations and normalized expression of genes regulating hepatic lipid and glucose metabolism. Moreover, dihydrocapsiate administration significantly improved gut morphology and altered gut microbial composition, resulting in reduced host energy availability. Collectively, these results indicate that dihydrocapsiate administration improved glucose tolerance, prevented adiposity and hepatic steatosis, as well as improved HFD-induced gut alterations, positing dihydrocapsiate as a potential food ingredient for the dietary management of HFD-induced metabolic alterations.
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    Involvement of Glucagon in Preventive Effect of Menthol Against High Fat Diet Induced Obesity in Mice
    (Frontiers, 2018-11) Khare, Pragyanshu
    Glucagon mediated mechanisms have been shown to play clinically significant role in energy expenditure. The present study was designed to understand whether pharmacological mimicking of cold using menthol (TRPM8 modulator) can induce glucagon-mediated energy expenditure to prevent weight gain and related complications. Acute oral and topical administration of TRPM8 agonists (menthol and icilin) increased serum glucagon concentration which was prevented by pre-treatment with AMTB, a TRPM8 blocker. Chronic administration of menthol (50 and 100 mg/kg/day for 12 weeks) to HFD fed animals prevented weight gain, insulin resistance, adipose tissue hypertrophy and triacylglycerol deposition in liver. These effects were not restricted to oral administration, but also observed upon the topical application of menthol (10% w/v). The metabolic alterations caused by menthol in liver and adipose tissue mirrored the known effects of glucagon, such as increased glycogenolysis and gluconeogenesis in the liver, and enhanced thermogenic activity of white and brown adipose tissue. Correlation analysis suggests a strong correlation between glucagon dependent changes and energy expenditure markers. Interestingly, in-vitro treatment of the serum of menthol treated mice increased energy expenditure markers in mature 3T3L1 adipocytes, which was prevented in the presence of non-competitive glucagon receptor antagonist, L-168,049, indicating that menthol-induced increase in serum glucagon is responsible for increase in energy expenditure phenotype. In conclusion, the present work provides evidence that glucagon plays an important role in the preventive effect of menthol against HFD-induced weight gain and related complications.
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    Allicin, a dietary trpa1 agonist, prevents high fat diet-induced dysregulation of gut hormones and associated complications
    (RSC, 2021) Khare, Pragyanshu
    Given the global epidemic of diabesity (co-existence of both diabetes and obesity), novel approaches that target gut hormone secretion and their modulation may offer the dual benefits of increased efficacy and limited side effects. In the present study, we tested the hypothesis that agonism of Transient Receptor Potential Ankyrin 1 (TRPA1), using a dietary activator, has a modulatory role in high fat diet (HFD)-induced dysregulation of post-prandial gut hormone responses and prevention of metabolic alterations. Methods and results. The effect of HFD on TRPA1 expression in different parts of the gut using immunohistochemistry, western blotting and RT-PCR was studied. Dietary TRPA1 agonist, Allicin Rich Garlic Juice (ARGJ), was co-administered along with HFD in mice for three months and various metabolic health parameters, relative gut hormone levels and inflammation were observed. The HFD caused substantial reduction in gut TRPA1 expression along with dysregulation in post-prandial normalization of gut hormone levels, particularly GLP-1, precipitating hunger phenotype, altered glucose homeostasis, hepatic inflammation and fat accumulation. TRPA1 agonism through ARGJ co-supplementation prevented HFD-induced dysregulation in post-prandial normalization of gut hormone levels and averted metabolic and inflammatory complications in peripheral tissues. Conclusion. Our findings provide evidence that ARGJ (diet-based TRPA1 agonism) can be employed as a feasible strategy, as nutraceuticals or food, to prevent HFD-induced metabolic complications.
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    Insulin sensitizing and cardioprotective effects of Esculetin and Telmisartan combination by attenuating Ang II mediated vascular reactivity and cardiac fibrosis
    (Elsevier, 2015-10) Gaikwad, Anil Bhanudas
    The combination of the angiotensin receptor blockers (ARBs) with other synthetic and natural molecules has been reported to have better safety profile and therapeutic efficacy in prevention of diabetes and its associated complications than their monotherapy. Driven by the aforementioned facts, this study was conceived to evaluate the potential additive effect of combination of Telmisartan and Esculetin in prevention of insulin resistance and associated cardiac fibrosis. Recently, we have reported that Esculetin prevented cardiovascular dysfunction associated with insulin resistance (IR) and type 2 diabetes. Insulin resistance was developed by high fat diet (HFD) feeding to Wistar rats. Telmisartan and Esculetin were administered at 10 mg/kg/day and 50 mg/kg/day doses (P.O, 2 weeks), respectively either alone or in combination. Plasma biochemical analyses, vascular reactivity and immunohistochemical experiments were performed to assess the beneficial effect of Telmisartan, Esculetin and their combination on insulin resistance and associated cardiac fibrosis. The study results showed that, co-administered Telmisartan and Esculetin ameliorated the pathological features like metabolic perturbation, morphometric alterations, vascular hyper responsiveness, extracellular matrix accumulation and the expression of fibronectin and TGF-β more effectively than monotherapy in HFD fed rats. Hence, the study urges us to conclude that the solution to IR and associated cardiovascular dysfunction may lie in the Telmisartan and Esculetin combination therapy.
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    [P2–130]: AR-A014418, A GSK-3β INHIBITOR, ATTENUATES ALZHEIMER'S- LIKE PATHOLOGY IN HIGH FAT DIET-INDUCED COGNITIVE DEFICIT IN MICE
    (Wiley, 2017-07) Taliyan, Rajeev
    Alzheimer's disease (AD) is characterized by the progressive deposition of fibrillar amyloid-β (Aβ) in the form of extracellular plaques and hyperphosphorylated tau as intraneuronal neuro fibrillary tangles (NFTs). Studies have reported that increased Glycogen synthase kinase-3β (GSK-3β) activity has been associated with hyper phosphorylation of tau. However, the molecular mechanisms of association still remain elusive. Thus, the present study was designed to explore the potential of GSK-3β inhibitor, AR-A014418 in high fat diet (HFD) induced cognitive impairment and AD like pathology.