Skeletal Muscle Angiopoietin-Like Protein 4 and Glucose Metabolism in Older Adults after Exercise and Weight Loss.

Guoyan Li,Hefang Zhang,Alice S Ryan

doi:10.3390/metabo10090354

Abstract

Angiopoietin-like protein 4 (ANGPTL4) is an adipokine that plays an important role in energy homoeostasis and lipid and lipoprotein metabolism. This study was designed to determine the effect of an exercise plus weight loss intervention on ANGPTL4 expression and its relationship with metabolic health. Thirty-five obese sedentary men (n = 18) and postmenopausal women (n = 17), (X ± SEM, age: 61 ± 1 years, BMI: 31.3 ± 0.7 kg/m2, VO2max: 21.7 ± 0.9 L/kg/min) completed a 6 month program of 3×/week aerobic exercise and 1×/week dietary instruction to induce weight loss (AEX + WL). Participants underwent vastus lateralis muscle biopsies, a hyperinsulinemic–euglycemic clamp, oral glucose tolerance tests and body composition testing. Basal skeletal muscle ANGPTL4 mRNA was lower in men than women (p < 0.01). Peroxisome proliferator-activated receptor (PPAR) alpha (PPARα) mRNA expression was higher in men than women (p < 0.05). There were no significance changes in serum or skeletal muscle ANGPTL4 (basal or insulin-stimulated) or muscle PPARα mRNA expression after AEX + WL. Muscle mRNA ANGPTL4 is correlated with serum ANGPTL4 (r = 0.41, p < 0.05), body fat (r = 0.64, p < 0.0001), and glucose utilization (r = 0.38, p < 0.05). AEX + WL does not change basal or insulin-stimulated skeletal muscle ANGPTL4 mRNA expression, suggesting other factors contribute to improved insulin sensitivity after the loss of body fat and improved fitness.

Highlights

Metabolites 2020, 10, 354 with type 2 diabetes mellitus compared with healthy adults [12] and circulating Angiopoietin-like protein 4 (ANGPTL4) levels were negatively associated with plasma glucose and insulin resistance by Homeostatic Model Assessment of Insulin Resistance (HOMA IR) in humans [12]
Serum or plasma ANGPTL4 levels are related to obesity and insulin resistance, its expression in skeletal muscle during basal conditions and hyperinsulinemia, and its relationship with insulin sensitivity, have not been well studied in older, generally healthy, adults, nor compared between men and women
Body weight decreased 8% (p < 0.001) with a decrease in the percentage of body fat of 11% (p < 0.001), a 17% decrease in total fat mass (p < 0.001), a 20% decrease in visceral adipose tissue (VAT), a 16% decrease in subcutaneous abdominal fat and a

Summary

Introduction

Angiopoietin-like protein 4 (ANGPTL4), a member of the angiogenin-like protein family, is expressed in a wide variety of tissues, such as liver, adipose tissue, skeletal muscle, placenta, small intestine, brain, thyroid, kidney, spleen, pituitary gland, hypothalamus and heart [1,2,3,4,5,6,7,8], while predominately expressed in the liver, adipose tissue and placenta [8,9,10] and induced in multitude of physiological conditions, such as fasting, hypoxic environments, pregnancy and lactation, adipocyte differentiation and exercise [1,3,4,11]. ANGPTL4 serum levels are significantly higher in adults with abnormal glucose tolerance and are associated with central and total obesity and insulin resistance by the Homeostatic Model Assessment of Insulin Resistance (HOMA IR) [13]. Metabolites 2020, 10, 354 with type 2 diabetes mellitus compared with healthy adults [12] and circulating ANGPTL4 levels were negatively associated with plasma glucose and insulin resistance by HOMA IR in humans [12]. Serum or plasma ANGPTL4 levels are related to obesity and insulin resistance, its expression in skeletal muscle during basal conditions and hyperinsulinemia, and its relationship with insulin sensitivity, have not been well studied in older, generally healthy, adults, nor compared between men and women

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