Short-term trivalent arsenic and hexavalent chromium exposures induce gut dysbiosis and transcriptional alteration in adipose tissue of mice.

Background: Inorganic arsenic [As(III)] and hexavalent chromium [Cr(VI)] can potentially affect metabolic functions. These heavy metal(s)/metalloids can also affect the gut microbial architecture which affects metabolic health. Here, we assessed the effects of short-term exposure of As(III) and Cr(VI) on key transcription factors in adipose tissues and on selected gut microbial abundances to understand the possible modulatory role of these toxicants on host metabolic health.

Allicin, a dietary trpa1 agonist, prevents high fat diet-induced dysregulation of gut hormones and associated complications.

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. The effect of HFD on TRPA1 expression in different parts of the gut using immunohistochemistry, western blotting and RT-PCR was studied.

Involvement of Glucagon in Preventive Effect of Menthol Against High Fat Diet Induced Obesity in Mice.

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.

Probiotic attributes and prevention of LPS-induced pro-inflammatory stress in RAW264.7 macrophages and human intestinal epithelial cell line (Caco-2) by newly isolated Weissella cibaria strains.

Probiotic lactic acid bacteria are known to modulate gut associated immune responses. Not many studies have reported on the role of Weissella species in preventing lipopolysaccharide (LPS) induced proinflammatory stress in murine macrophages as well as in human intestinal epithelial cells (Caco-2). Therefore, the present study was taken up to evaluate the probiotic attributes of four newly isolated Weissella strains (two each from fermented dosa batter and a human infant faecal sample); these attributes are cholesterol reduction, adhesion to Caco-2 cells and mucin and their ability to prevent LPS-induced nitric oxide and proinflammatory cytokine (IL-6, IL-1β and TNFα) production by the murine macrophages and IL-8 production by the human epithelial cells.

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.

Purpose: 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.

Finger millet arabinoxylan protects mice from high-fat diet induced lipid derangements, inflammation, endotoxemia and gut bacterial dysbiosis.

Arabinoxylan (AX), a non-starch polysaccharide extracted from cereals such as wheat, rice and millets, is known to impart various health promoting effects. Our earlier study suggested that finger millet (FM) could ameliorate high fat diet (HFD)-induced metabolic derangements. The present study is aimed to evaluate the effect of FM-AX supplementation, a key bioactive from finger millet, on HFD-induced metabolic and gut bacterial derangements.

Isomalto-oligosaccharides, a prebiotic, functionally augment green tea effects against high fat diet-induced metabolic alterations via preventing gut dysbacteriosis in mice.

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.

Kodo millet whole grain and bran supplementation prevents high-fat diet induced derangements in a lipid profile, inflammatory status and gut bacteria in mice.

The protective role of kodo millet whole grain and bran supplementation in diet induced obesity has not been investigated. Here we have studied the role of kodo millet supplementation in age matched Swiss albino mice that were randomly divided into groups and fed their respective diets for 16 weeks. A high fat diet increased weight gain, reduced glucose tolerance, increased serum lipids, altered hepatic and adipocyte gene expression and caused dysbiosis in the intestinal beneficial bacteria.

Cinnamaldehyde supplementation prevents fasting-induced hyperphagia, lipid accumulation, and inflammation in high-fat diet-fed mice.

Cinnamaldehyde, a bioactive component of cinnamon, is increasingly gaining interest for its preventive and therapeutic effects against metabolic complications like type-2 diabetes. This study is an attempt to understand the effect of cinnamaldehyde in high-fat diet (HFD)-associated increase in fasting-induced hyperphagia and related hormone levels, adipose tissue lipolysis and inflammation, and selected cecal microbial count in mice. Cinnamaldehyde, at 40 µM dose, prevented lipid accumulation and altered gene expression toward lipolytic phenotype in 3T3-L1 preadipocyte cell lines.

Resistance to the Beneficial Metabolic Effects and Hepatic Antioxidant Defense Actions of Fibroblast Growth Factor 21 Treatment in Growth Hormone-Overexpressing Transgenic Mice.

Fibroblast growth factor 21 (FGF21) modulates a diverse range of biological functions, including glucose and lipid metabolism, adaptive starvation response, and energy homeostasis, but with limited mechanistic insight. FGF21 treatment has been shown to inhibit hepatic growth hormone (GH) intracellular signaling. To evaluate GH axis involvement in FGF21 actions, transgenic mice overexpressing bovine GH were used.

Microarray based gene expression analysis of murine brown and subcutaneous adipose tissue: significance with human.

Background: Two types of adipose tissues, white (WAT) and brown (BAT) are found in mammals. Increasingly novel strategies are being proposed for the treatment of obesity and its associated complications by altering amount and/or activity of BAT using mouse models.

Methodology/principle Findings: The present study was designed to: (a) investigate the differential expression of genes in LACA mice subcutaneous WAT (sWAT) and BAT using mouse DNA microarray, (b) to compare mouse differential gene expression with previously published human data; to understand any inter- species differences between the two and (c) to make a comparative assessment with C57BL/6 mouse strain.

Female PAPP-A knockout mice are resistant to metabolic dysfunction induced by high-fat/high-sucrose feeding at middle age.

Longevity and aging are influenced by common intracellular signals of the insulin/insulin-like growth factor (IGF)-1 pathway. Abnormally high levels of bioactive IGF-1 increase the development of various cancers and may contribute to metabolic diseases such as insulin resistance. Enhanced availability of IGF-1 is promoted by cleavage of IGF binding proteins (IGFBPs) by proteases, including the pregnancy-associated plasma protein-A (PAPPA).

GH/STAT5 signaling during the growth period in livers of mice overexpressing GH.

GH/STAT5 signaling is desensitized in the liver in adult transgenic mice overexpressing GH; however, these animals present greater body size. To assess whether the STAT5 pathway is active during the growth period in the liver in these animals, and how signaling modulators participate in this process, growing transgenic mice and normal siblings were evaluated. STAT5 does not respond to an acute GH-stimulus, but displays higher basal phosphorylation in the livers of growing GH-overexpressing mice.

Specific suppression of insulin sensitivity in growth hormone receptor gene-disrupted (GHR-KO) mice attenuates phenotypic features of slow aging.

In addition to their extended lifespans, slow-aging growth hormone receptor/binding protein gene-disrupted (knockout) (GHR-KO) mice are hypoinsulinemic and highly sensitive to the action of insulin. It has been proposed that this insulin sensitivity is important for their longevity and increased healthspan. We tested whether this insulin sensitivity of the GHR-KO mouse is necessary for its retarded aging by abrogating that sensitivity with a transgenic alteration that improves development and secretory function of pancreatic β-cells by expressing Igf-1 under the rat insulin promoter 1 (RIP::IGF-1).

Finger millet bran supplementation alleviates obesity-induced oxidative stress, inflammation and gut microbial derangements in high-fat diet-fed mice.

Several epidemiological studies have shown that the consumption of finger millet (FM) alleviates diabetes-related complications. In the present study, the effect of finger millet whole grain (FM-WG) and bran (FM-BR) supplementation was evaluated in high-fat diet-fed LACA mice for 12 weeks. Mice were divided into four groups: control group fed a normal diet (10 % fat as energy); a group fed a high-fat diet; a group fed the same high-fat diet supplemented with FM-BR; a group fed the same high-fat diet supplemented with FM-WG.

Capsaicin induces "brite" phenotype in differentiating 3T3-L1 preadipocytes.

Objective: Targeting the energy storing white adipose tissue (WAT) by pharmacological and dietary means in order to promote its conversion to energy expending "brite" cell type holds promise as an anti-obesity approach. Present study was designed to investigate/revisit the effect of capsaicin on adipogenic differentiation with special reference to induction of "brite" phenotype during differentiation of 3T3-L1 preadipocytes.

Methods: Multiple techniques such as Ca2+ influx assay, Oil Red-O staining, nutrigenomic analysis in preadipocytes and matured adipocytes have been employed to understand the effect of capsaicin at different doses.

Capsaicin-induced transcriptional changes in hypothalamus and alterations in gut microbial count in high fat diet fed mice.

Obesity is a global health problem and recently it has been seen as a growing concern for developing countries. Several bioactive dietary molecules have been associated with amelioration of obesity and associated complications and capsaicin is one among them. The present work is an attempt to understand and provide evidence for the novel mechanisms of anti-obesity activity of capsaicin in high fat diet (HFD)-fed mice.

Preservation of blood glucose homeostasis in slow-senescing somatotrophism-deficient mice subjected to intermittent fasting begun at middle or old age.

Poor blood glucose homeostatic regulation is common, consequential, and costly for older and elderly populations, resulting in pleiotrophically adverse clinical outcomes. Somatotrophic signaling deficiency and dietary restriction have each been shown to delay the rate of senescence, resulting in salubrious phenotypes such as increased survivorship. Using two growth hormone (GH) signaling-related, slow-aging mouse mutants we tested, via longitudinal analyses, whether genetic perturbations that increase survivorship also improve blood glucose homeostatic regulation in senescing mammals.

Interaction of growth hormone receptor/binding protein gene disruption and caloric restriction for insulin sensitivity and attenuated aging.

The correlation of physiological sensitivity to insulin ( vis-à-vis glycemic regulation) and longevity is extensively established, creating a justifiable gerontological interest on whether insulin sensitivity is causative, or even predictive, of some or all phenotypes of slowed senescence (including longevity). The growth hormone receptor/ binding protein gene-disrupted (GHR-KO) mouse is the most extensively investigated insulin-sensitive, attenuated aging model. It was reported that, in a manner divergent from similar mutants, GHR-KO mice fail to respond to caloric restriction (CR) by altering their insulin sensitivity.

Expression of multiple Transient Receptor Potential channel genes in murine 3T3-L1 cell lines and adipose tissue.

Background: Calcium and its signaling have a role in adipogenesis. Transient Receptor Potential (TRP) channels are non-selective cation channels with a high permeability to calcium.

Methods: In the present study the expression of multiple TRP channels on mouse 3T3-L1 preadipocyte and adipocyte cells, white (WAT) and brown (BAT) adipose tissues was investigated using real time PCR (RT-PCR).

Duration of rapamycin treatment has differential effects on metabolism in mice.

The evolutionarily conserved target of rapamycin (TOR) signaling controls growth, metabolism, and aging. In the first robust demonstration of pharmacologically-induced life extension in mammals, longevity was extended in mice treated with rapamycin, an inhibitor of mechanistic TOR (mTOR). However, detrimental metabolic effects of rapamycin treatment were also reported, presenting a paradox of improved survival despite metabolic impairment.

Role of transient receptor potential channels in adipocyte biology.

The transient receptor potential (TRP) channel superfamily is a family of 28 nonselective cation channels expressed on the plasma membrane with a high permeability to calcium. Role of TRP channels, especially TRP vanilloid 1, TRP ankyrin 1 and TRP melastatin 8, is widely documented in nociception. During the last few years, there has been a consistent increase in reports indicating the presence and significance of these channels in different tissues including bladder, skin, respiratory system and brain.

Hepatocellular alterations and dysregulation of oncogenic pathways in the liver of transgenic mice overexpressing growth hormone.

Growth hormone (GH) overexpression throughout life in transgenic mice is associated with the development of liver tumors at old ages. The preneoplastic pathology observed in the liver of young adult GH-overexpressing mice is similar to that present in humans at high risk of hepatic cancer. To elucidate the molecular pathogenesis underlying the pro-oncogenic liver pathology induced by prolonged exposure to elevated GH levels, the activation and expression of several components of signal transduction pathways that have been implicated in hepatocellular carcinogenesis were evaluated in the liver of young adult GH-transgenic mice.