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New Publications from the NORC at Washington University, St. Louis

May 25, 2021

New Publications from the NORC at Washington University, St. Louis Beals JW, Smith GI, Shankaran M, Fuchs A, Schweitzer GG, Yoshino J, Field T, Matthews M, Nyangau E, Morozov D, Mittendorfer B, Hellerstein MK, Klein S.  Increased adipose tissue fibrogenesis, not impaired expandability, is associated with nonalcoholic fatty liver disease. Hepatology (in press). Yoshino M, Yoshino J, Kayser BD, Patti G, Franczyk MP, Mills KF, Sindelar M, Patterson BW, Imai S-I, Klein S.  Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.  Science (in press). Fuchs A, Samovski D, Smith GI, Cifarelli V, Farabi S, Yoshino J, Pietka T, Chang … Read More »

Categories: Featured News, News, Publications Tags: Washington University St. Louis

The muscle anabolic effect of protein ingestion during a hyperinsulinaemic euglycaemic clamp in middle‐aged women is not caused by leucine alone

October 18, 2019

Abstract It has been suggested that leucine is primarily responsible for the increase in muscle protein synthesis (MPS) after protein ingestion because leucine uniquely activates the mTOR‐p70S6K signalling cascade. We tested this hypothesis by measuring muscle p‐mTORSer2448, p‐p70S6KThr389 and p‐eIF2αSer51, as well as protein turnover (by stable isotope labelled amino acid tracer infusion in conjunction with leg arteriovenous blood and muscle tissue sampling), in 28 women who consumed either 0.45 g protein kg−1 fat‐free mass (containing 0.0513 g leucine kg−1 fat‐free mass) or a control drink (n = 14) or 0.0513 g leucine kg−1 fat‐free mass or a control drink (n = 14) during a hyperinsulinaemic‐euglycaemic clamp procedure … Read More »

Categories: Featured News, News, Publications Tags: Washington University St. Louis

Effect of Progressive Weight Loss on Lactate Metabolism: a Randomized Controlled Trial

October 18, 2019

Abstract Objective Lactate is an intermediate of glucose metabolism that has been implicated in the pathogenesis of insulin resistance. This study evaluated the relationship between glucose kinetics and plasma lactate concentration ([LAC]) before and after manipulating insulin sensitivity by progressive weight loss. Methods Forty people with obesity (BMI=37.9±4.3 kg/m2) were randomized to weight maintenance (n=14) or weight loss (n=19). Subjects were studied before and after 6 months of weight maintenance and before and after 5%, 11% and 16% weight loss. A hyperinsulinemic-euglycemic clamp procedure in conjunction with [6,6-2H2]glucose tracer infusion was used to assess glucose kinetics. Results At baseline, fasting … Read More »

Categories: Featured News, News, Publications Tags: Washington University St. Louis

Diurnal Variation in PDK4 Expression Is Associated With Plasma Free Fatty Acid Availability in People

October 18, 2019

Abstract Context Many biological pathways involved in regulating substrate metabolism display rhythmic oscillation patterns. In rodents, clock genes regulate circadian rhythms of metabolic genes and substrate metabolism. However, the interrelationships among substrate metabolism, metabolic genes, and clock genes have not been fully explored in people. Objective We tested the hypothesis that the diurnal expression pattern of pyruvate dehydrogenase kinase 4 (PDK4), a key metabolic enzyme involved in fuel switching between glucose and free fatty acids (FFAs), is associated with plasma FFA concentration and clock genes. Design and Methods We analyzed peripheral blood mononuclear cells (PBMCs), subcutaneous adipose tissue, and plasma … Read More »

Categories: Featured News, News, Publications Tags: Washington University St. Louis

Modeling the Effect of Cigarette Smoke on Hexose Utilization in Spermatocytes

July 31, 2016

Abstract We set out to determine whether the addition of an aryl hydrocarbon receptor (AHR) antagonist has an effect on glucose/fructose utilization in the spermatocyte when exposed to cigarette smoke condensate (CSC). We exposed male germ cells to 5 and 40 μg/mL of CSC ± 10 μmol/L of AHR antagonist at various time points. Immunoblot expression of specific glucose/fructose transporters was compared to control. Radiolabeled uptake of 2-deoxyglucose (2-DG) and fructose was also performed. Spermatocytes utilized fructose nearly 50-fold more than 2-DG. Uptake of 2-DG decreased after CSC + AHR antagonist exposure. Glucose transporters (GLUTs) 9a and 12 declined after … Read More »

Categories: Publications Tags: Washington University St. Louis

Plasma Biomarker of Dietary Phytosterol Intake

February 10, 2015

Abstract Dietary phytosterols, plant sterols structurally similar to cholesterol, reduce intestinal cholesterol absorption and have many other potentially beneficial biological effects in humans. Due to limited information on phytosterol levels in foods, however, it is difficult to quantify habitual dietary phytosterol intake (DPI). Therefore, we sought to identify a plasma biomarker of DPI. Citation Lin X, Racette SB, Ma L, Wallendorf M, Spearie CA, Ostlund RE Jr. Plasma biomarker of dietary phytosterol intake. PLoS One. 2015 Feb 10;10(2):e0116912. PMID: 25668184; PMCID: PMC4323197. Read More PLoS One Research Details Research Center: Washington University, St. Louis

Categories: Publications Tags: Washington University St. Louis

Peroxisomal Lipid Synthesis Regulates Inflammation by Sustaining Neutrophil Membrane Phospholipid Composition and Viability

January 6, 2015

Abstract Fatty acid synthase (FAS) is altered in metabolic disorders and cancer. Conventional FAS null mice die in utero so effects of whole body inhibition of lipogenesis following development are unknown. Inducible global knockout of FAS (iFASKO) in mice was lethal due to a disrupted intestinal barrier and leukopenia. Conditional loss of FAS was associated with the selective suppression of granulopoiesis without disrupting granulocytic differentiation. Transplantation of iFASKO bone marrow into wild type mice followed by Cre induction resulted in selective neutrophil depletion but not death. Impaired lipogenesis increased ER stress and apoptosis in neutrophils by preferentially decreasing peroxisome-derived membrane … Read More »

Categories: Publications Tags: Washington University St. Louis

Effect of Roux-en-Y Gastric Bypass and Laparoscopic Adjustable Gastric Banding on Branched-Chain Amino Acid Metabolism

August 1, 2013

Abstract It has been hypothesized that a greater decline in circulating branched-chain amino acids (BCAAs) after weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery than after calorie restriction alone has independent effects on glucose homeostasis, possibly by decreased signaling through the mammalian target of rapamycin (mTOR). We evaluated plasma BCAAs and their C3 and C5 acylcarnitine metabolites, muscle mTOR phosphorylation, and insulin sensitivity (insulin-stimulated glucose Rd) in obese subjects before and after ~20% weight loss induced by RYGB (n = 10, BMI 45.6 ± 6.7 kg/m(2)) or laparoscopic adjustable gastric banding (LAGB) (n = 10, BMI 46.5 ± 8.8 … Read More »

Categories: Publications Tags: Washington University St. Louis

Intrahepatic Diacylglycerol Content is Directly Associated with Hepatic Insulin Resistance in Obese Subjects

June 1, 2013

Abstract Data from studies in animal models indicate that certain lipid metabolites, particularly diacylglycerol, ceramide, and acylcarnitine, disrupt insulin action. We evaluated the relationship between the presence of these metabolites in the liver (assessed by mass spectrometry) and hepatic insulin sensitivity (assessed using a hyperinsulinemic-euglycemic clamp with stable isotope tracer infusion) in 16 obese adults (body mass index, 48 ± 9 kg/m²). There was a negative correlation between insulin-mediated suppression of hepatic glucose production and intrahepatic diacylglycerol (r = -0.609; P = .012), but not with intrahepatic ceramide or acylcarnitine. These data indicate that intrahepatic diacylglycerol is an important mediator … Read More »

Categories: Publications Tags: Washington University St. Louis