Somatostatin signaling and the regulation of growth and metabolism in fish

The study of the somatostatins (SS) signaling system in fish has provided important information about the structure, function, and evolution of SSs and their receptors. The SS signaling system elicits widespread biological actions via multiple hormone variants, numerous receptor subtypes, and a variety of signal transduction pathways. SSs alter growth via both direct and indirect actions, including inhibiting growth hormone release at the pituitary, decreasing hepatic GH sensitivity, and lowering plasma IGF-I levels. Metabolism also is significantly influenced by SSs. SSs stimulate the breakdown of energy stores and influences digestion, food intake, nutrient absorption, and food conversion both directly and through the modulation of other hormonal systems. The study of fish, which display a diversity of habitat types and life history forms, reveals that the SS signaling system helps regulate energy partitioning and integrate metabolism with growth and other biological processes.     

Elevation of blood lipids in hepatocyte-specific fatty acid transport 4-deficient mice fed with high glucose diets

Fatty acid transport protein4 (FATP4) is upregulated in acquired and central obesity and its polymorphisms are associated with blood lipids and insulin resistance. Patients with FATP4 mutations and mice with global FATP4 deletion exhibit skin abnormalities characterized as ischthyosis prematurity syndrome (IPS). Cumulating data have shown that an absence of FATP4 increases the levels of cellular triglycerides (TG). However, FATP4 role and consequent lipid and TG metabolism in the hepatocyte is still elusive. Here, hepatocyte-specific FATP4 deficient (Fatp4^L?/?) mice were generated. When fed with chow, these mutant mice displayed no phenotypes regarding blood lipids. However when fed low-fat/high-sugar (HS) or high-fat/high-sugar (HFS) for 12?weeks, Fatp4^L?/? mice showed a significant increase of plasma TG, free fatty acids and glycerol when compared with diet-fed control mice. Interestingly, Fatp4^L?/? mice under HS diet had lower body and liver weights and they were not protected from HFS-induced body weight gain and hepatic steatosis. Male mutant mice were more sensitive to HFS diet than female mutant mice. Glucose intolerance was observed only in female Fatp4^L?/? mice fed with HS diet. Lipidomics analyses revealed that hepatic phospholipids were not disturbed in mutant mice under both diets. Thus, hepatic FATP4 deletion rendered an increase of blood lipids including glycerol indicating a preferential fatty-acid channeling to TG pools that are specifically available for lipolysis. Our results imply a possible risk of hyperlipidemia as a result of abnormal metabolism in liver in IPS patients with FATP4 mutations who consume high-sugar diets.     

Ginkgolide C reduced oleic acid-induced lipid accumulation in HepG2 cells

Ginkgolide C, isolated from Ginkgo biloba, is a diterpene lactone that has multiple biological functions and can improve Alzheimer disease and platelet aggregation. Ginkgolide C also inhibits adipogenesis in 3T3-L1 adipocytes. The present study evaluated whether ginkgolide C reduced lipid accumulation and regulated the molecular mechanism of lipogenesis in oleic acid-induced HepG2 hepatocytes. HepG2 cells were treated with 0.5?mM oleic acid for 48?h to induce a fatty liver cell model. Then, the cells were exposed to various concentrations of ginkgolide C for 24?h. Staining with Oil Red O and the fluorescent dye BODIPY 493/503 revealed that ginkgolide C significantly reduced excessive lipid accumulation in HepG2 cells. Ginkgolide C decreased peroxisome proliferator-activated receptor γ and sterol regulatory element-binding protein 1c to block the expression of fatty acid synthase. Ginkgolide C treatment also promoted the expression of adipose triglyceride lipase and the phosphorylation level of hormone-sensitive lipase to enhance the decomposition of triglycerides. In addition, ginkgolide C stimulated CPT-1 to activate fatty acid β-oxidation, significantly increased sirt1 and phosphorylation of AMP-activated protein kinase (AMPK), and decreased expression of acetyl-CoA carboxylase for suppressed fatty acid synthesis in hepatocytes. Taken together, our results suggest that ginkgolide C reduced lipid accumulation and increased lipolysis through the sirt1/AMPK pathway in oleic acid-induced fatty liver cells.     

Anti-obesity action of INDUS810, a natural compound from Trigonella foenum-graecum: AMPK-dependent lipolysis effect in adipocytes

ObjectiveWe investigated the anti-obesity effect and underlying action mechanism of INDUS810 isolated from Trigonella foenum-graecum L. (Fabaceae), an annual herb commonly known as fenugreek and reported to have hypocholesterolemic, antidiabetic, anticancer and gastroprotective properties.MethodsFor obese animal study, 4-week old mice were fed with normal diet or high-fat diet together with or without intraperitoneal injection of INDUS810 (200 mg/kg) twice per week for 15 weeks. 3T3-L1 cells were used to study action mechanism of INDUS810 in adipocyte differentiation and lipid metabolism.ResultsWe found that INDUS810 can reduce high-fat diet-induced weight increase in epididymal white adipose tissue, interscapular brown adipose tissue and liver, as well as serum levels of total cholesterol and low-density lipoprotein cholesterol. Moreover, the insulin sensitivity was significantly improved in INDUS810-treated obese mice. In 3T3-L1 adipocytes, we found that INDUS810 could inhibit lipid accumulation at either differentiating or mature stages, and increase lipolysis activity in mature adipocytes. Additionally, INDUS810 has no effects on cell viability nor the expressions of adipocyte differentiation markers like fatty acid synthase, peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α. In contrast, INDUS810 can increase protein levels of peroxisome proliferator-activated receptor α, peroxisome-proliferator-activated receptor-γ co-activator 1β, sirtuin 1 and sirtuin 3. Of note, INDUS810 can activate adenosine monophosphate-activated protein kinase, which leads to the reduction of lipid contents in adipocytes.ConclusionOur in vitro and in vivo studies suggest that INDUS810 is a potential anti-obesity agent, and this action depends on activate adenosine monophosphate-activated protein kinase activation.     

Medium-chain fatty acid reduces lipid accumulation by regulating expression of lipid-sensing genes in human liver cells with steatosis

Accumulation of lipids in the liver can lead to cell dysfunction and steatosis, an important factor in pathogenesis causing non-alcoholic fatty liver disease. The mechanisms related to lipid deposition in the liver, however, remain poorly understood. This study was aimed to investigate the effects of medium-chain fatty acid (MCFA) on the lipolysis and expression of lipid-sensing genes in human liver cells with steatosis. A cellular steatosis model, which is suitable to experimentally investigate the impact of fat accumulation in the liver, was established in human normal liver cells (LO2 cells) with a mixture of free fatty acids (oleate/palmitate, 2:1) at 200?μm for 24?h incubation. MCFA was found to down-regulate expression of liver X receptor-α, sterol regulatory element binding protein-1, acetyl-CoA carboxylase, fatty acid synthase, CD 36 and lipoprotein lipase in this cellular model, and have positive effects on adipose triglyceride lipase and hormone-sensitive lipase. These results suggest that MCFA may reduce lipid accumulation by regulating key lipid-sensing genes in human liver cells with steatosis.     

Controlling lipolysis through steric surfactants: new insights on the controlled degradation of submicron emulsions after oral and intravenous administration

In this work we have investigated how steric surfactants influence the metabolic degradation of emulsions (lipolysis). To do so, we have prepared submicron emulsions stabilized with Pluronic F68, Pluronic F127, Myrj 52 or Myrj 59, four non-ionic surfactants with key differences on their structure. Submicron emulsions have been prepared also with mixtures of these surfactants with different proportions between them. Then, in vitro methods have been applied to analyze the lipolysis of these emulsions, both under duodenal and intravenous conditions, to simulate lipolysis after oral and intravenous administration. Our results show that the properties of the surfactant influence dramatically the lipolysis rates observed both under duodenal and intravenous conditions, e.g., intravenous lipolysis was completely blocked when Pluronic F127 was used, while it was almost complete within 6 h when using Myrj 52. The reason for this seems to be the steric hindrance that the surfactant produces around the droplet and at the interface. As a result, we can modify the lipolysis patterns by changing some characteristics of the surfactant, or by varying the proportion between two surfactants in a mixture. These findings may be applied in the development of novel strategies to rationally design submicron emulsions as lipophilic drug carriers.     

Body shaping with acoustic wave therapy AWT®/EPAT®: Randomized,controlled study on 14 subjects

Abstract

Introduction: Reduction of localised adiposities by non invasive means is a very frequent request among the female and male population. Objective: The objective of this study is to demonstrate the efficacy and safety of AWT^®, combining two different mechanical waves, planar AWT and radial AWT during the same session, in volume reduction of saddle bags in women. Methods: Treatment was performed on the saddle bag areas of 14 female patients, with the CELLACTOR^® SC1 (Storz Medical AG, Tägerwilen, Switzerland) using extracorporeal pulse activation technology, EPAT^®. This device includes two handpieces, the C-ACTOR^® and the D-ACTOR^®. Within 4 weeks, eight AWT^® treatment sessions have been performed with both applicators. Follow-up visits were performed 1, 4 and 12 weeks after the last treatment. Results: Measurements with the ultrasound system clearly demonstrate a significant diminution in the subcutaneous fat layer thickness and a reduction of the averaged circumference of thighs. Conclusions: This study, although performed on a small number of patients, tends to show the safety and efficacy of AWT^® in treating localized fat areas in a non-invasive way. There is also an additional benefit for patients in reducing the cellulite appearance and improving the skin firmness at the same time by using AWT^®.     

Activation of muscarinic M-3 receptor may decrease glucose uptake and lipolysis in adipose tissue of rats

Role of muscarinic receptor in the regulation of glucose uptake or lipolysis in adipose tissue remained unclear. In epididymal white adipose tissue (WAT) isolated from Wistar rats, we observed that acetylcholine (ACh) attenuated the insulin-stimulated glucose uptake and the release of glycerol from WAT in a concentration-dependent manner. Using the blockade of specific antagonists, both actions of ACh were characterized mainly due to an activation of M3 receptors. In the presence of various inhibitors for PLC–PKC pathway, ACh-decreased glucose uptake was also reversed. Taken together, these results suggest that muscarinic M3 receptor is involved in the regulation of glucose uptake and/or lipolysis in adipose tissue.     

Adipose tissue-liver axis in alcoholic liver disease

Alcoholic liver disease(ALD) remains an important health problem worldwide. The disease spectrum is featured by early steatosis, steatohepatitis(steatosis with inflammatory cells infiltration and necrosis), with some individuals ultimately progressing to fibrosis/cirrhosis. Although the disease progression is well characterized, no effective therapies are currently available for the treatment in humans. The mechanisms underlying the initiation and progression of ALD are multifactorial and complex. Emerging evidence supports that adipose tissue dysfunction contributes to the pathogenesis of ALD. In the first part of this review, we discuss the mechanisms whereby chronic alcohol exposure contributed to adipose tissue dysfunction, including cell death, inflammation and insulin resistance. It has been long known that aberrant hepatic methionine metabolism is a major metabolic abnormality induced by chronic alcohol exposure and plays an etiological role in the pathogenesis of ALD. The recent studies in our group documented the similar metabolic effect of chronic alcohol drinking on methionine in adipose tissue. In the second part of this review, we also briefly discuss the recent research progress in the field with a focus on how abnormal methionine metabolism in adipose tissue contributes to adipose tissue dysfunction and liver damage.