GPR41 is reportedly expressed in murine adipose tissue and mediates short chain fatty acid (SCFA)-stimulated leptin secretion by activating Galpha(i). Here, we agree with a contradictory report finding no expression of tissue. Nevertheless, the presence adenosine deaminase to minimise Galpha(i) signalling via A1 receptor, SCFA stimulated adipocytes from wild-type but not knockout mice. Expression GPR43 was reduced Acetate butyrate mesenteric adipocytes, consistent mediation response rather...

Context: Chemerin is a new adipokine associated with obesity and the metabolic syndrome. Gene expression levels of chemerin were elevated in adipose depots obese compared lean animals was markedly during differentiation fibroblasts into mature adipocytes. Objective: The objective study to identify factors that affect regulation potential function using genetics approach. Design, Setting, Patients, Intervention: Plasma measured subjects from San Antonio Family Heart Study, large family-based...

SCFA are produced in the gut by bacterial fermentation of undigested carbohydrates. Activation Gα i -protein-coupled receptor GPR41 β-cells and sympathetic ganglia inhibits insulin secretion increases outflow, respectively. A possible role stimulating leptin adipocytes is disputed. In present study, we investigated energy balance glucose homoeostasis knockout mice fed on a standard low-fat or high-fat diet. When diet, body fat mass was raised tolerance impaired male but not female compared...

Cannabinoid type-1 (CB1) receptor inverse agonists improve type 2 diabetes and dyslipidaemia but were discontinued due to adverse psychiatric effects. Δ(9)-Tetrahydrocannabivarin (THCV) is a neutral CB1 antagonist producing hypophagia body weight reduction in lean mice. We investigated its effects dietary-induced (DIO) genetically (ob/ob) obese mice.We performed two dose-ranging studies DIO mice; study 1: 0.3, 1, 2.5, 5 12.5 mg kg(-1), oral twice daily for 30 days 2: 0.1, 0.5, 2.5 oral, once...

The potentially beneficial effects of pomegranate peel (PPE), flower (PFE) and seed oil (PSO) extracts, in comparison with rosiglitazone, on adiposity, lipid profile, glucose homoeostasis, as well the underlying inflammatory mechanisms, were examined high-fat high-sucrose (HF/HS) diet-induced obese (DIO) mice.Body weight, body fat, energy expenditure, food liquid intake, blood glucose, plasma levels insulin, lipids cytokines measured.After two weeks, PSO (2 ml/kg/day) rosiglitazone (3...

Free fatty acid receptor 1 (FFA1 or GPR40) enhances glucose-stimulated insulin secretion from pancreatic β-cells and currently attracts high interest as a new target for the treatment of type 2 diabetes. We here report discovery highly potent FFA1 agonist with favorable physicochemical pharmacokinetic properties. The compound efficiently normalizes glucose tolerance in diet-induced obese mice, an effect that is fully sustained after 29 days chronic dosing.

The free fatty acid receptor 1 (FFA1, also known as GPR40) mediates enhancement of glucose-stimulated insulin secretion and is emerging a new target for the treatment type 2 diabetes. Several FFA1 agonists are known, but majority these suffer from high lipophilicity. We have previously reported agonist 3 (TUG-424). here describe continued structure-activity exploration optimization this compound series, leading to discovery more potent 40, with low lipophilicity, excellent in vitro metabolic...

Background Salvia officinalis (sage) is a native plant to the Mediterranean region and has been used for long time in traditional medicine various diseases. We investigated possible anti-diabetic, anti-inflammatory anti-obesity effects of sage methanol (MetOH) extract nutritional mouse model obesity, inflammation insulin resistance, as well its on lipolysis lipogenesis 3T3-L1 cells. Methods Diet-induced obese (DIO) mice were treated five weeks with (100 400 mg kg −1 /day bid), or...

The literature is unclear on whether the adipokine chemerin has pro- or anti-inflammatory properties plays any role in aetiology of type 2 diabetes obesity. To address these questions, and particular potential agonists antagonists receptor CMKLR1 treatment obesity, we studied metabolic phenotypes both male female, knockout heterozygote mice. We also investigated changes plasma levels gene mRNA content adipose tissue models obesity diabetes, response to fasting administration insulin...

The effect of IL-1β on cytokine and chemokine production by human preadipocytes has been examined. Preadipocytes were incubated with IL-1β, release was measured at 24 h protein arrays, while the expression cytokine/chemokine genes assessed qPCR 4 h. stimulated secretion multiple cytokines/chemokines, including IL-6, IL-8, IL-10, IL-13, MCP-4, TNFα IP-10. IL-10 not released un-stimulated preadipocytes, IL-6 exhibited greatest response to (453-fold increase). IL-16 IL-12p40 did respond IL-1β....

Cognitive health is of great interest to society, with neuroinflammation and systemic inflammation age-related risk factors that are linked declines in cognitive performance. Several botanical ingredients have been suggested benefits this area including Salvia officinalis (sage), which has shown anti-inflammatory effects exhibited promising improvements multiple human studies. The current study demonstrates for S. across a broad set vitro models cells, adds further evidence support...

Regulation of the expression GPCR fatty acid receptor genes has been examined in human adipocytes differentiated culture. TNFα and IL-1β induced a marked reduction GPR120 expression, mRNA level falling 17-fold at 24 h incubated with TNFα. In contrast, GPR84 was dramatically increased by these cytokines (>500-fold for 4 h); GPR41 also stimulated. Rosiglitazone did not affect but increased. Dexamethasone, insulin, linoleic docosahexaenoic acids (DHA), TUG891 (GPR120 agonist) had little effect...

Previous studies by Tisdale et al. have reported that zinc-α(2)-glycoprotein (ZAG (AZGP1)) reduces body fat content and improves glucose homeostasis the plasma lipid profile in Aston (ob/ob) mice. It has been suggested this might be mediated via agonism of β(3)- possibly β(2)-adrenoceptors. We compared effects dosing recombinant human ZAG (100 μg, i.v.) BRL35135 (0.5 mg/kg, i.p.), which is rodents a 20-fold selective relative to β(2)-adrenoceptor agonist, given once daily for 10 days male...

The aim of the study was to investigate involvement adipokines eotaxin-3, MIP-1β, and MCP-4 in obesity related comorbidities modification their circulating levels after bariatric surgery. Eighty severely obese subjects 20 normal-weight controls were included study. Circulating MCP-4, main clinical, biochemical, instrumental parameters for evaluation cardiovascular metabolic profile determined at baseline 10 months Within group baseline, eotaxin-3 higher males than females smokers non-smokers...

Primary cultures of rat hippocampal neurons were prepared and exposed to increasing concentrations a peroxyl radical-generator, 2,2′-azobis 2 amidinopropane (AAPH). Addition AAPH (20 or 50 mM) the medium caused decrease in cell viability an increase number apoptotic cells. Values for nucleosomes obtained using ELISA technique. “Factor F,” indicator enrichment nucleosomes, was found be directly proportional neuronal apoptoses. extract Ginkgo biloba (Egb 761; 5–20 μg/ml) ginkgolide B (one its...

The role of IL-1β in regulating the expression and secretion cytokines chemokines by human adipocytes was examined. Adipocytes were incubated with for 4 or 24 h. a panel 84 cytokine/chemokine genes probed using PCR arrays. stimulated >30 on arrays; 15 showed >100-fold increases mRNA at h including CSF3, CXCL1, CXCL2, CXCL12 IL8. CSF3 exhibited 10 000-fold increase ADIPOQ among whose inhibited. Protein arrays used to examine cytokines/chemokines from adipocytes. multiple MCP-1, IL-8, IP-10,...

Salvia officinalis L. (sage), and Chamaemelum nobile (L.) (chamomile) have been used traditionally to treat various inflammatory conditions. Our study aims investigate the anti-inflammatory properties of both plant extracts in IL-1β-stimulated neuroblastoma cells (SK-N-SH) human subcutaneous mature adipocytes, as well their potential protective effects against adipocytes conditioned media (ACM)-induced neuro-inflammation. Human were treated with 5 μg/ml (low dose: LD) 50 (high HD) each...

Abstract Background A high-sugar or/and high-fat diets is a major risk factors for obesity. However, increased fruit and vegetable intake has been recently linked to obesity prevention. The aim of the present study was investigate preventive effects pomegranate leaves (PL), juice (PJ) peel (PP) extracts, on insulin resistance oxidative stress in high fat fructose diet-induced obese rats. Methods Obesity rats induced by consumption diet saturated (HFD) long period (12 weeks). Results Compared...

ABSTRACT Context Chemerin is a new adipokine associated with obesity and the metabolic syndrome. Gene expression levels of chemerin were elevated in adipose depots obese compared lean animals was markedly during differentiation fibroblasts into mature adipocytes. Objective To identify factors that affect regulation potential function using genetics approach. Design, setting, patients intervention Plasma measured subjects from San Antonio Family Heart Study (SAFHS), large family-based genetic...

The role of IL-1β in regulating the expression extracellular matrix (ECM) and cell adhesion genes human adipocytes has been examined. Adipocytes differentiated culture were incubated with for 4 or 24 h RNA probed PCR arrays 84 ECM genes. Treatment resulted changes at one both time points ∼50% by arrays, majority being down-regulated. Genes whose was down-regulated included those encoding several collagen chains integrin subunits. In contrast, induced substantial increases (>10-fold) ICAM1,...

Kv1 channels are shaker-related potassium that influence insulin sensitivity. Kv1.3(-/-) mice protected from diet-induced resistance and some studies suggest Kv1.3 inhibitors provide similar protection. However, it is unclear whether blockade of in adipocytes or skeletal muscle increases glucose uptake. There no evidence the related channel Kv1.5 has any on sensitivity its expression adipose tissue not been reported. PAP-1 a selective inhibitor Kv1.3, with 23-fold, 32-fold 125-fold lower...

The insulin-sensitizing phytocannabinoid, Δ(9)-tetrahydrocannabivarin (THCV) can signal partly via G-protein coupled receptor-55 (GPR55 behaving as either an agonist or antagonist depending on the assay). cannabinoid receptor type 1 (CB1R) inverse rimonabant is also a GPR55 under some conditions. Previous studies have shown varied effects of deletion energy balance and glucose homeostasis in mice. contribution signalling to metabolic THCV has been little studied.In preliminary experiment,...