Ceramide concentrations in liver, plasma, and very low-density lipoproteins of humans with severe obesity.

We investigated the relationships between ceramide species concentrations in liver, plasma and very low-density lipoproteins (VLDL) particles of humans with obesity as well as the relationships between hepatic fat content and hepatic ceramide concentrations and proportional distribution. Twenty-five obese (body mass index >35 kg/m ) adults participated in this study. Plasma, VLDL and hepatocellular ceramide concentrations were measured by liquid chromatography/tandem mass spectrometry.

Adipose Tissue Inflammation Is Not Related to Adipose Insulin Resistance in Humans.

The role of adipose tissue (AT) inflammation in AT function in humans is unclear. We tested whether AT macrophage (ATM) content, cytokine gene expression, and senescent cell burden (markers of AT inflammation) predict AT insulin resistance measured as the insulin concentration that suppresses lipolysis by 50% (IC50). We studied 86 volunteers with normal weight or obesity at baseline and a subgroup of 25 volunteers with obesity before and after weight loss.

Senescent cells in human adipose tissue: A cross-sectional study.

Objective: Adipose tissue (AT) senescence is associated with AT dysfunction in rodents, but little is known about human AT senescence. The study goal was to define the distribution of senescent cells in two subcutaneous depots and understand relationships with adiposity and inflammation.

Methods: Sixty-three volunteers (48 females) underwent abdominal and femoral subcutaneous fat biopsies.

Adipocyte Proteins and Storage of Endogenous Fatty Acids in Visceral and Subcutaneous Adipose Tissue in Severe Obesity.

Objective: This study tested whether substrate concentrations or fatty acid storage proteins predict storage of endogenous lipids in visceral adipose tissue (VAT) and upper body subcutaneous adipose tissue (UBSQ) fat.

Methods: The day prior to surgery, 25 patients undergoing bariatric procedures received an infusion of autologous [1- C]triolein-labeled very low-density lipoprotein (VLDL) particles, and during surgery, they received a continuous [U- C]palmitate infusion/bolus [9,10- H]palmitate tracer. VAT and UBSQ fat were collected to measure VLDL-triglyceride (TG) storage, direct free fatty acid (FFA) storage rates, CD36 content, lipoprotein lipase (LPL), acyl-CoA synthetase, diacylglycerol acetyl-transferase, and glycerol-3-phosphate acyltransferase activities.

Insulin-Stimulated Muscle Glucose Uptake and Insulin Signaling in Lean and Obese Humans.

Purpose: Skeletal muscle is the primary site for insulin-stimulated glucose disposal, and muscle insulin resistance is central to abnormal glucose metabolism in obesity. Whether muscle insulin signaling to the level of Akt/AS160 is intact in insulin-resistant obese humans is controversial.

Methods: We defined a linear range of insulin-stimulated systemic and leg glucose uptake in 14 obese and 14 nonobese volunteers using a 2-step insulin clamp (Protocol 1) and then examined the obesity-related defects in muscle insulin action in 16 nonobese and 25 obese male and female volunteers matched for fitness using a 1-step, hyperinsulinemic, euglycemic clamp coupled with muscle biopsies (Protocol 2).

A Lipidomic Analysis of Docosahexaenoic Acid (22:6, ω3) Mediated Attenuation of Western Diet Induced Nonalcoholic Steatohepatitis in Male Mice.

Nonalcoholic fatty liver disease (NAFLD) is a major public health problem worldwide. NAFLD ranges in severity from benign steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and primary hepatocellular cancer (HCC). Obesity and type 2 diabetes mellitus (T2DM) are strongly associated with NAFLD, and the western diet (WD) is a major contributor to the onset and progression of these chronic diseases.

Hepatic Fatty Acid Balance and Hepatic Fat Content in Humans With Severe Obesity.

Objective: Nonalcoholic fatty liver disease can lead to hepatic inflammation/damage. Understanding the physiological mechanisms that contribute to excess hepatic lipid accumulation may help identify effective treatments.

Design: We recruited 25 nondiabetic patients with severe obesity scheduled for bariatric surgery.

The Soluble Fiber α-Cyclodextrin Does Not Increase the Fecal Losses of Dietary Fat in Adults-A Double-Blind, Randomized, Placebo-Controlled, Crossover Trial.

Background: α-Cyclodextrin (α-CD), a soluble dietary fiber, may improve abnormal plasma lipids and promote weight loss. Preliminary evidence suggests that it may exert these effects by binding dietary fat and reducing absorption; this has not been tested in humans.

Objective: The primary objective was to test whether supplemental α-CD increases fecal content of dietary lipid in humans.

Omega-3 polyunsaturated fatty acids as a treatment strategy for nonalcoholic fatty liver disease.

Obese and type 2 diabetic (T2DM) patients have a high prevalence of nonalcoholic fatty liver disease (NAFLD). NAFLD is a continuum of chronic liver diseases ranging from benign hepatosteatosis to nonalcoholic steatohepatitis (NASH), cirrhosis and primary hepatocellular cancer (HCC). Because of its strong association with the obesity epidemic, NAFLD is rapidly becoming a major public health concern worldwide.

Docosahexaenoic acid blocks progression of western diet-induced nonalcoholic steatohepatitis in obese Ldlr-/- mice.

Background: Nonalcoholic fatty liver disease (NAFLD) is a major public health concern in western societies. Nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, is characterized by hepatic steatosis, inflammation, oxidative stress and fibrosis. NASH is a risk factor for cirrhosis and hepatocellular carcinoma.

Is Western Diet-Induced Nonalcoholic Steatohepatitis in Ldlr-/- Mice Reversible?

Background: Nonalcoholic fatty liver disease (NAFLD) is a major public health burden in western societies. The progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), is characterized by hepatosteatosis, inflammation, oxidative stress, and hepatic damage that can progress to fibrosis and cirrhosis; risk factors for hepatocellular carcinoma. Given the scope of NASH, validating treatment protocols (i.

Docosahexaenoic acid attenuates Western diet-induced hepatic fibrosis in Ldlr-/- mice by targeting the TGFβ-Smad3 pathway.

DHA (22:6,ω3), but not EPA (20:5,ω3), attenuates Western diet (WD)-induced hepatic fibrosis in a Ldlr(-/-) mouse model of nonalcoholic steatohepatitis. We examined the molecular basis for the differential effect of dietary EPA and DHA on WD-induced hepatic fibrosis. DHA was more effective than EPA at preventing WD-induced effects on hepatic transcripts linked to fibrosis, including collagen 1A1 (Col1A1), transforming growth factor-β (TGFβ) signaling and proteins involved in remodeling the extracellular matrix, including metalloproteases, tissue inhibitors of metalloproteases, and lysyl oxidase subtypes.

Impact of dietary fat on the development of non-alcoholic fatty liver disease in Ldlr-/- mice.

The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased in parallel with central obesity and is now the most common chronic liver disease in developed countries. NAFLD is defined as excessive accumulation of lipid in the liver, i.e.

Fatty acid elongase-5 (Elovl5) regulates hepatic triglyceride catabolism in obese C57BL/6J mice.

Nonalcoholic fatty liver disease is a major public health concern in the obese and type 2 diabetic populations. The high-fat lard diet induces obesity and fatty liver in C57BL/6J mice and suppresses expression of the PPAR-target gene, FA elongase 5 (Elovl5). Elovl5 plays a key role in MUFA and PUFA synthesis.