Adipose tissue-derived adipokines play important roles in controlling systemic insulin sensitivity and energy balance. Our recent efforts to identify novel metabolic mediators produced by adipose tissue have led the discovery of a highly conserved family secreted proteins, designated as C1q/TNF-related proteins 1-10 (CTRP1 -10). However, physiological functions regulated CTRPs are largely unknown. Here we provide first vivo functional characterization CTRP3. We show that circulating levels...

Objective— Reduced plasma adiponectin (APN) in diabetic patients is associated with endothelial dysfunction. However, APN knockout animals manifest modest systemic dysfunction unless metabolically challenged. The protein family CTRPs (C1q/TNF-related proteins) has recently been identified as paralogs and some CTRP members share APN′s metabolic regulatory function. the vasoactive properties of remain completely unknown. Methods Results— vasoactivity currently murine was assessed aortic...

Members of the C1q/TNF family play important and diverse roles in immune, endocrine, skeletal, vascular, sensory systems. Here, we identify characterize CTRP13, a new extremely conserved member family. CTRP13 is preferentially expressed by adipose tissue brain mice predominantly humans. Within mouse tissue, largely cells stromal vascular compartment. Due to sexually dimorphic expression patterns, female have higher transcript circulating levels than males. are elevated obese male mice,...

CTRP9 is a secreted multimeric protein of the C1q family and closest paralog insulin-sensitizing adipokine, adiponectin. The metabolic function this adipose tissue-derived plasma remains largely unknown. Here, we show that circulating levels are downregulated in diet-induced obese mice upregulated upon refeeding. Overexpressing resulted lean dramatically resisted weight gain induced by high-fat diet, through decreased food intake increased basal metabolism. Enhanced fat oxidation transgenic...

CTRP3 is a secreted plasma protein of the C1q family that helps regulate hepatic gluconeogenesis and downregulated in diet-induced obese state. However, role regulating lipid metabolism has not been established. Here, we used transgenic mouse model to address potential function ameliorating high-fat metabolic stress. Both wild-type mice fed diet showed similar body weight gain, food intake, energy expenditure. Despite adiposity upon obesity (DIO), were strikingly resistant development...

Background The mammalian otoconial membrane is a dense extracellular matrix containing bio-mineralized otoconia. This structure provides the mechanical stimulus necessary for hair cells of vestibular maculae to respond linear accelerations and gravity. In teleosts, Otolin required proper anchoring otolith crystals sensory maculae. Otoconia detachment subsequent entrapment in semicircular canals can result benign paroxysmal positional vertigo (BPPV), common form which molecular basis unknown....

Reduced skeletal muscle microvessel density (MVD) in the obese Zucker rat (OZR) model of metabolic syndrome is a function chronic reduction vascular nitric oxide (NO) bioavailability. Previous studies suggest that exercise can improve NO bioavailability and reduce inflammation low may be associated with impaired angiogenic responses via increased matrix metalloproteinase (MMP)-2 MMP-9 activity. As such, we hypothesized (EX) would increase OZR blunt microvascular rarefaction through reduced...

The obese Zucker rat (OZR) is a model of metabolic syndrome, which has lower skeletal muscle size than the lean (LZR). Because satellite cells are essential for postnatal growth, this study was designed to determine whether reduced cell proliferation contributes mass in OZR vs. LZR. Satellite determined by constant-release 5-bromo-2-deoxyuridine (BrdU) pellet that placed subcutaneously each animal. proliferation, as BrdU incorporation, significantly attenuated control soleus and plantaris...

C1q/TNF-related proteins (CTRPs) are a family of secreted regulators glucose and lipid metabolism. Here, we describe CTRP11, novel phylogenetically conserved member the C1q family. Our studies revealed that white brown adipose major tissues express its expression is acutely regulated by changes in metabolic state. Within tissue, CTRP11 primarily expressed stromal vascular cells. As multimeric protein, forms disulfide-linked oligomers. Although N-terminal Cys-28 Cys-32 dispensable for...

Metabolic dysfunction in skeletal muscle is a major contributor to the development of type 2 diabetes. Endurance exercise training has long been established as an effective means directly restore glucose and lipid uptake metabolism. However, addition direct effects on lipids, there renewed interest ability coordinate metabolic activity other tissues, such adipose tissue liver. The purpose this study was examine endurance expression level two novel muscle-derived secreted factors, or...

C1q/TNF-related protein 3 (CTRP3) is a secreted hormone that modulates hepatic glucose and lipid metabolism. Its circulating levels are reduced in human rodent models of obesity, metabolic state accompanied by chronic low-grade inflammation. Recent studies have demonstrated an anti-inflammatory role for recombinant CTRP3 attenuating LPS-induced systemic inflammation, its deficiency markedly exacerbates inflammation mouse model rheumatoid arthritis. We used genetic to explore the...

Mitochondrial apoptosis and apoptotic signaling modulations by aerobic training were studied in cardiac skeletal muscles of obese Zucker rats (OZR), a rodent model metabolic syndrome. Comparisons made between left ventricle, soleus, gastrocnemius from OZR ( n = 16) aged-matched lean (LZR; that untrained 8) or aerobically trained on treadmill for 9 wk 8). Cardiac Bcl-2 protein expression levels ∼50% lower the compared with LZR, no difference either muscles. Bax similar LZR. Furthermore,...

CTRP2 is a secreted plasma protein of the C1q family that enhances glycogen deposition and fat oxidation in cultured myotubes. Its vivo metabolic function, however, has not been established. We show here acute chronic perturbations induced by fasting or high-fat feeding up-regulated mRNA expression Ctrp2 white adipose tissue without affecting its circulating levels. generated transgenic mouse model with elevated levels to determine function vivo. When fed low-fat diet, wild-type mice...

Neuropeptides are ubiquitous in both mammals and invertebrates play essential roles regulation modulation of many developmental physiological processes through activation G-protein-coupled-receptors (GPCRs). However, the mechanisms by which neuropeptides regulate specific neural function behaviors remain undefined. Here we investigate functions Drosulfakinin (DSK), Drosophila homolog vertebrate neuropeptide cholecystokinin (CCK), is most abundant central nervous system. We provide...

Storage of excess calories as triglycerides is central to obesity and its associated disorders. Glycerol-3-phosphate acyltransferases (GPATs) catalyze the initial step in acylglyceride syntheses, including triglyceride synthesis. We utilized a novel small-molecule GPAT inhibitor, FSG67, investigate metabolic consequences systemic pharmacological inhibition lean diet-induced obese (DIO) mice. FSG67 administered intraperitoneally decreased body weight energy intake, without producing...

We used Ligand-receptor glycocapture technology with TriCEPS™-based ligand-receptor capture (LRC-TriCEPS; Dualsystems Biotech AG). The LRC-TriCEPS experiment CTRP3-FLAG protein as ligand and insulin a control was performed on the H4IIE rat hepatoma cell line.Initial analysis demonstrated efficient coupling of TriCEPS to CTRP3. Further, flow cytometry (FACS) successful oxidation crosslinking CTRP3-TriCEPS Insulin-TriCEPS complexes surface glycans. Demonstrating utility under these conditions,...

Migraine and other primary headache disorders affect a large population cause debilitating pain. Establishing animal models that display behavioral correlates of long-lasting ongoing headache, the most common disabling symptom migraine, is vital for elucidation disease mechanisms identification drug targets. We have developed mouse model using dural application capsaicin along with mixture inflammatory mediators (IScap) to simulate induction episode. This elicited intermittent head-directed...

C1q TNF Related Protein 3 (CTRP3) is a novel adipose tissue derived secreted factor, or adipokine, which has been linked to number of beneficial biological effects on metabolism, inflammation, and survival signaling in variety tissues. However, very little known about CTRP3 regards human health. The purpose this project was examine circulating levels clinical population, patients with symptoms requiring heart catheterization order identify the presence obstructive coronary artery disease...

Insulin resistance is a primary characteristic of type 2 diabetes. Several lines evidence suggest that accumulation free fatty acids in skeletal muscle may at least part contribute to insulin and be linked mitochondrial dysfunction, leading apoptosis. Palmitate treatment several cell vitro results apoptosis inhibits protein kinase B (Akt) activity response insulin. However, the role Bax Bcl-2 regulating palmitate-induced has not been well studied. Therefore, purpose this study was determine...