Suresh T. Mathews

Fetuin-A (Fet-A) is a liver-secreted phosphorylated protein, known to impair insulin signaling, which has been shown to be associated with obesity, insulin resistance, and incident diabetes. Fet-A interacts with the insulin-stimulated insulin receptor (IR) and inhibits IR tyrosine kinase activity and glucose uptake. It has been shown that high glucose increases Fet-A expression through the ERK1/2 signaling pathway. However, factors that downregulate Fet-A expression and their potential mechanisms are unclear. We examined the effect of AMP-activated protein kinase (AMPK) on high-glucose induced Fet-A expression in HepG2 cells, Hep3B cells and primary rat hepatocytes. High glucose increased Fet-A and phosphorylated (Ser312) fetuin-A (pFet-A) expression, which are known to impair insulin signaling. AICAR-induced AMPK activation significantly down-regulated high glucose-induced Fet-A expression and secretion of pFet-A while treatment with Compound C (AMPK inhibitor), SB202190 (p38 MAPK inhibitor) or p38 MAPK siRNA transfection prevented AICAR-induced downregulation of Fet-A expression. In addition, activation of p38 MAPK, by anisomycin, decreased the hepatic expression of Fet-A. Further, we our studies have shown that short-term effect of AICAR-treatment on Fet-A expression was mediated by proteosomal degradation, and long-term treatment of AICAR was associated with decrease in hepatic expression of C/EBP beta, an important transcription factor involved in the regulation of Fet-A. Taken together, our studies implicate a critical role for AMPK-p38 MAPK-C/EBPb-ubiquitin-proteosomal axis in the regulation of the expression of hepatic Fet-A.

Serum Fet‐A was transiently elevated immediately after a single bout of exercise. and restored to Pre Ex levels 24 h after a single bout of exercise. Furthermore, serum Fet‐AAUC, pFet‐AAUC, glucoseAU...

Objective: Phosphorylated fetuin‐A (pFet‐A) inhibits insulin action and has been shown to be associated with obesity and insulin resistance. The objective of this cohort study was to assess the effect of incremental body weight loss on alterations in serum pFet‐A and indexes of insulin sensitivity.Methods: A total of 16 men with obesity attained a targeted weight loss of 8% to 10% of their initial body weight by achieving an energy expenditure/deficit of 2,000 to 2,500 kcal/wk. Anthropometric assessments and blood samples were obtained every 4 weeks. Weight loss was calculated and partitioned as 2% to 4%, 4% to 6%, 6% to 8%, and 8% to 10% compared with initial body weight.Results: Targeted body weight loss of 8% to 10% decreased serum pFet‐A, pFet‐A:Fet‐A ratio, fasting insulin, log(homeostasis model assessment of insulin resistance), quantitative insulin sensitivity check index, adipose insulin resistance, and insulin resistance index significantly. Percent changes in serum pFet‐A were associated with percent changes in indexes of insulin sensitivity. Unlike insulin sensitivity indexes, which were altered starting with 6% to 8% weight loss, serum pFet‐A levels were significantly decreased by 19.6% starting with 2% to 4% weight loss and decreased by 25.6%, 36.8%, and 42.3% with 4% to 6%, 6% to 8%, and 8% to 10% weight loss, respectively.Conclusions: This study reports for the first time that the insulin‐sensitizing effects of moderate weight loss are associated with a reduction in serum pFet‐A levels.

Fetuin-A (Fet-A), a hepatokine associated with insulin resistance, obesity, and incident type 2 diabetes, is shown to exist in both phosphorylated and dephosphorylated forms in circulation. However, studies on fetuin-A phosphorylation status in insulin-resistant conditions and its functional significance are limited. We demonstrate that serum phosphofetuin-A (Ser312) levels were significantly elevated in high-fat diet-induced obese mice, insulin-resistant Zucker diabetic fatty rats, and in individuals with obesity who are insulin resistant. Unlike serum total fetuin-A, serum phosphofetuin-A was associated with body weight, insulin, and markers of insulin resistance. To characterize potential mechanisms, fetuin-A was purified from Hep3B human hepatoma cells. Hep3B Fet-A was phosphorylated (Ser312) and inhibited insulin-stimulated glucose uptake and glycogen synthesis in L6GLUT4 myoblasts. Furthermore, single (Ser312Ala) and double (Ser312Ala + Ser120Ala) phosphorylation-defective Fet-A mutants were without effect on glucose uptake and glycogen synthesis in L6GLUT4 myoblasts. Together, our studies demonstrate that phosphorylation status of Fet-A (Ser312) is associated with obesity and insulin resistance and raise the possibility that Fet-A phosphorylation may play a role in regulation of insulin action.

Coenzyme Q₁₀ (CoQ₁₀), an endogenously produced compound, is found in all human cells. Within the mitochondria, it plays a substantial role in energy production by acting as a mobile electron carrier in the electron transport chain. Outside the mitochondria, it acts as an excellent antioxidant by sequestering free radicals and working synergistically with other antioxidants, including vitamin E. Dietary contribution is limited, making endogenous production the primary source for optimal function. Now widely available as an over-the-counter supplement, CoQ₁₀ has gained attention for its possible therapeutic use in minimizing the outcomes of certain metabolic diseases, notably cardiovascular disease, diabetes, neurodegenerative disease, and cancer. Research has shown positive results in subjects supplemented with CoQ₁₀, especially in relation to upregulating antioxidant capability. Emerging research suggests beneficial effects of CoQ₁₀ supplementation in individuals on statin medications. CoQ₁₀ supplementation in individuals participating in strenuous exercise seems to exert some beneficial effects, although the data are conflicting with other types of physical activity. This broad review of current CoQ₁₀ literature, while outlining its physiological/functional significance in health and disease conditions, also offers a dietitian’s perspective on its potential use as a supplement in the promotion of health and management of disease conditions.

P1 Impact of antioxidant-enriched nutrient bar supplementation on the serum antioxidant markers and physical fitness components of track and field athletes Lalitha Ramaswamy, Supriya Velraja P2 The effects of phosphatidic acid supplementation on fitness levels in resistance trained women Guillermo Escalante, Phil Harvey, Michelle Alencar, Bryan Haddock P3 The effects of phosphatidic acid supplementation on cardiovascular risk factors in resistance trained men Phil Harvey, Guillermo Escalante, Michelle Alencar, Bryan Haddock P4 The efficacy of sodium bicarbonate supplementation on physical capacity and selected biochemical markers in elite wrestlers Krzysztof Durkalec-Michalski, Jan Jeszka, Bogna Zawieja, Tomasz Podgórski P5 Effects of different nutritional strategies in hydration and physical performance in healthy well-trained males Ana Paula Trussardi Fayh, Alexandre Hideki Okano, Amanda Maria de Jesus Ferreira P6 Reduction of plasma creatine concentrations as an indicator of improved bioavailability Ralf Jäger, Martin Purpura, Roger C Harris P7 Effect of three different breakfast meals on energy intake and nutritional status in college-age women Molly M. Krause, Kiley A. Lavanger, Nina O. Allen, Allison E. Lieb, Katie A. Mullen, Joan M. Eckerson P8 Accuracy of the ASA24® Dietary Recall system for assessing actual dietary intake in normal weight college-age women. Kiley A. Lavanger, Molly M. Krause, Nina O. Allen, Allison E. Lieb, Katie A. Mullen, Joan M. Eckerson P9 β-aminoisobutyric acid does not regulate exercise induced UCP-3 expression in skeletal muscle Elisa Morales, Jeffrey Forsse, Thomas Andre, Sarah McKinley, Paul Hwang, Grant Tinsley, Mike Spillane, Peter Grandjean, Darryn Willoughby P10 The ability of collegiate football athletes to adhere to sport-specific nutritional recommendations A. Jagim, G. Wright, J. Kisiolek, M. Meinking, J. Ochsenwald, M. Andre, M.T. Jones, J. M. Oliver P11 A single session of low-volume high intensity interval exercise improves appetite regulation in overweight men Victor Araújo Ferreira, Daniel Costa de Souza, Victor Oliveira Albuquerque dos Santos, Rodrigo Alberto Vieira Browne, Eduardo Caldas Costa, Ana Paula Trussardi Fayh P12 Acute effects of oral peppermint oil ingestion on exercise performance in moderately-active college students Suresh T. Mathews, Haley D. Bishop, Clara R. Bowen, Yishan Liang, Emily A. West, Rebecca R. Rogers, Mallory R. Marshall, John K. Petrella P13 Associations in body fat and liver triglyceride content with serum health markers in sedentary and exercised rats fed a ketogenic diet, Western diet or standard chow over a 6-week period A. Maleah Holland, Wesley C. Kephart, Petey W. Mumford, C. Brooks Mobley, Ryan P. Lowery, Jacob M. Wilson, Michael D. Roberts P14 Physiological changes following competition in male and female physique athletes: A pilot study Eric T. Trexler, Katie R. Hirsch, Bill I. Campbell, Meredith G. Mock, Abbie E. Smith-Ryan P15 Relationship between cognition and hydration status in college students at a large Southwestern university Kate Zemek, Carol Johnston P16 Whey protein-derived exosomes increase protein synthesis in C2C12 myotubes C. Brooks Mobley, Petey W. Mumford, David D. Pascoe, Christopher M. Lockwood, Michael E. Miller, Michael D. Roberts P17 The effect of three different energy drinks on 1.5-mile running performance, oxygen consumption, and perceived exertion Gabriel J. Sanders, Willard Peveler, Brooke Warning, Corey A. Peacock P18 The Ketogenic diet improves rotarod performance in young and older rats Wesley C. Kephart, Petey W. Mumford, Ryan P. Lowery, Michael D. Roberts, Jacob M. Wilson P19 Absorption of bonded arginine silicate compared to individual arginine and silicon components David Sandler, Sara Perez Ojalvo, James Komorowski P20 Effects of a high (2.4 g/kg) vs. low/moderate (1.2 g/kg) protein intake on body composition in aspiring female physique athletes engaging in an 8-week resistance training program Bill I. Campbell, Danielle Aguilar, Andres Vargas, Laurin Conlin, Amey Sanders, Paola Fink-Irizarry, Layne Norton, Ross Perry, Ryley McCallum, Matthew R. Wynn, Jack Lenton P21 Effects of a high (2.4 g/kg) vs. low/moderate (1.2 g/kg) protein intake on maximal strength in aspiring female physique athletes engaging in an 8-week resistance training program Bill I. Campbell, Chris Gai, Seth Donelson, Shiva Best, Daniel Bove, Kaylee Couvillion, Jeff Dolan, Dante Xing, Kyshia Chernesky, Michael Pawela, Andres D. Toledo, Rachel Jimenez P22 Monitoring of female collegiate athletes over a competitive season reveals changes in nutritional biomarkers M. Rabideau, A. Walker, J. Pellegrino, M. Hofacker, B. McFadden, S. Conway, C. Ordway, D. Sanders, R. Monaco, M. S. Fragala, S. M. Arent P23 Comparison of prediction equations to indirect calorimetry in men and women athletes Jason D. Stone, Andreas Kreutzer, Jonathan M. Oliver, Jacob Kisiolek, Andrew R. Jagim P24 Regional variations in sweat-based electrolyte loss and changes in plasma electrolyte content in Division I female athletes over the course of a competitive season M. Hofacker, A. Walker, J. Pellegrino, M. Rabideau, B. McFadden, S. Conway, D. Sanders, C. Ordway, R. Monaco, M. S. Fragala, S. M. Arent P25 In-season changes in plasma amino acid levels in Division I NCAA female athletes Ozlem Tok, Joseph K. Pellegrino, Alan J. Walker, David J. Sanders, Bridget A. McFadden, Meaghan M. Rabideau, Sean P. Conway, Chris E. Ordway, Marissa Bello, Morgan L. Hofacker, Nick S. Mackowski, Anthony J. Poyssick, Eddie Capone, Robert M. Monaco, Maren S. Fragala, Shawn M. Arent P26 Effects of a ketogenic diet with exercise on serum markers of bone metabolism, IGF-1 and femoral bone mass in rats Petey W. Mumford, A. Maleah Holland, Wesley C. Kephart, Ryan P. Lowery, C. Brooks Mobley, Romil K. Patel, Annie Newton, Darren T. Beck, Michael D. Roberts, Jacob M. Wilson, Kaelin C. Young P27 Casein supplementation in trained men...

Current literature shows an association of diabetes and secondary complications with chronic inflammation. Evidence of these immunological changes include altered levels of cytokines and chemokines, changes in the numbers and activation states of various leukocyte populations, apoptosis, and fibrosis during diabetes. Therefore, treatment of diabetes and its complications may include pharmacological strategies to reduce inflammation. Apart from anti-inflammatory drugs, various hypoglycemic agents have also been found to reduce inflammation that could contribute to improved outcomes. Extensive studies have been carried out with thiazolidinediones (peroxisome proliferator-activated receptor- agonist), dipeptidyl peptidase-4 inhibitors, and metformin (AMP-activated protein kinase activator) with each of these classes of compounds showing moderate-to-strong anti-inflammatory action. Sulfonylureas and alpha glucosidase inhibitors appeared to exert modest effects, while the injectable agents, insulin and glucagon-like peptide-1 receptor agonists, may improve secondary complications due to their anti-inflammatory potential. Currently, there is a lack of clinical data on anti-inflammatory effects of sodium–glucose cotransporter type 2 inhibitors. Nevertheless, for all these glucose-lowering agents, it is essential to distinguish between anti-inflammatory effects resulting from better glucose control and effects related to intrinsic anti-inflammatory actions of the pharmacological class of compounds.

Fetuin inhibits insulin-induced insulin receptor (IR) autophosphorylation and tyrosine kinase activity in vitro, in intact cells, and in vivo. The fetuin gene (AHSG) is located on human chromosome 3q27, recently identified as a susceptibility locus for type 2 diabetes and the metabolic syndrome. Here, we explore insulin signaling, glucose homeostasis, and the effect of a high-fat diet on weight gain, body fat composition, and glucose disposal in mice carrying two null alleles for the gene encoding fetuin, Ahsg (B6, 129-Ahsg^tm1Mbl). Fetuin knockout (KO) mice demonstrate increased basal and insulin-stimulated phosphorylation of IR and the downstream signaling molecules mitogen-activated protein kinase (MAPK) and Akt in liver and skeletal muscle. Glucose and insulin tolerance tests in fetuin KO mice indicate significantly enhanced glucose clearance and insulin sensitivity. Fetuin KO mice subjected to euglycemic-hyperinsulinemic clamp show augmented sensitivity to insulin, evidenced by increased glucose infusion rate (P = 0.077) and significantly increased skeletal muscle glycogen content (P < 0.05). When fed a high-fat diet, fetuin KO mice are resistant to weight gain, demonstrate significantly decreased body fat, and remain insulin sensitive. These data suggest that fetuin may play a significant role in regulating postprandial glucose disposal, insulin sensitivity, weight gain, and fat accumulation and may be a novel therapeutic target in the treatment of type 2 diabetes, obesity, and other insulin-resistant conditions.