Abstract
The prevalence and incidence of metabolic syndrome is reaching pandemic proportions worldwide, thus warranting an intensive search for novel preventive and treatment strategies. Recent studies have identified a number of soluble factors secreted by adipocytes and myocytes (adipo-/myokines), which link sedentary life style, abdominal obesity, and impairments in carbohydrate and lipid metabolism. In this review, we discuss the metabolic roles of the recently discovered myokine β-aminoisobutyric acid (BAIBA), which is produced by skeletal muscle during physical activity. In addition to physical activity, the circulating levels of BAIBA are controlled by the mitochondrial enzyme alanine: glyoxylate aminotransferase 2 (AGXT2), which is primarily expressed in the liver and kidneys. Recent studies have shown that BAIBA can protect from diet-induced obesity in animal models. It induces transition of white adipose tissue to a “beige” phenotype, which induces fatty acids oxidation and increases insulin sensitivity. While the exact mechanisms of BAIBA-induced metabolic effects are still not well understood, we discuss some of the proposed pathways. The reviewed data provide new insights into the connection between physical activity and energy metabolism and suggest that BAIBA might be a potential novel drug for treatment of the metabolic syndrome and its cardiovascular complications.
Highlights
Manifestations of the metabolic syndrome such as abdominal obesity, dyslipidemia, insulin resistance, and hypertension, remain to be the major risk factors for diabetes and cardiovascular diseases
The goal of this review is to summarize the current knowledge about BAIBA metabolism and its recently discovered protective biological effects, and to discuss the implications of these recently discovered pathways for prevention and treatment of the metabolic syndrome and its complications
These results suggest that BAIBA may affect lipid metabolism and insulin sensitivity via restoration of leptin levels in patients with reduced production of this hormone [49]
Summary
Manifestations of the metabolic syndrome such as abdominal obesity, dyslipidemia, insulin resistance, and hypertension, remain to be the major risk factors for diabetes and cardiovascular diseases. The more recent hypothesis explains the development of obesity-associated metabolic disturbances through alteration in the production of myokines, or “exercise factors”, by skeletal myocytes [18]. Secretion of these molecules, including interleukin (IL)-6, IL-15, and irisin, is strongly upregulated during aerobic physical exercise [18,19]. Elevation of IL-15 leads to a decline of fat mass in mice [20], and recently discovered myokine irisin induces “browning” of white adipose tissue (the differentiation of resident progenitor cells in white adipose tissue into morphologically and physiologically distinct brown-like adipocytes) and results in increased energy expenditure, body weight reduction, and improvement of diet-induced insulin resistance in mice [21]. The goal of this review is to summarize the current knowledge about BAIBA metabolism and its recently discovered protective biological effects, and to discuss the implications of these recently discovered pathways for prevention and treatment of the metabolic syndrome and its complications
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