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.

Apolipoprotein A‐I (ApoA‐I) is the main functional protein component of human high‐density lipoproteins. ApoA‐I shows various anti‐inflammatory and atheroprotective properties toward macrophages; however, endogenous apoA‐I expression has not been investigated in macrophages. We have shown that endogenous apoA‐I gene is expressed in human macrophages at both mRNA and protein levels. Endogenous ApoA‐I is localized in intracellular vesicles and at the external side of the plasma membrane in association with ATP‐binding cassette transporter A1 (ABCA1) and lipid rafts in macrophages. We have shown that endogenous ApoA‐I stabilizes ABCA1, moreover, down‐regulation of ApoA‐I by siRNA results in an increase of Toll‐like receptor 4 (TLR4) mRNA and membrane surface protein expression, as well as an enhancement of bacterial lipopolysaccharide (LPS)‐induced expression of tumor necrosis factor‐α (TNF‐α), interleukin 1β (IL‐1β), and inducible nitric oxide synthase (NOS2) genes in human macrophages. TNF‐α stimulates ApoA‐I expression and secretion (1.2±0.2 vs. 4.3±0.9 ng/mg total protein) in macrophages. Obtained results suggest that endogenous ApoA‐I has anti‐inflammatory properties, presumably due to ABCA1 stabilization in macrophages; these results elucidate the cell type‐specific mechanism of the TNF‐α‐mediated regulation of apoA‐I gene expression in monocytes and macrophages.—Mogilenko, D. A., Orlov, S. V., Trulioff, A. S., Ivanov, A. V., Nagumanov, V. K., Kudriavtsev, I. V., Shavva, V. S., Tanyanskiy, D. A., Perevozchikov, A. P. Endogenous apolipoprotein A‐I stabilizes ATP‐binding cassette transporter A1 and modulates Toll‐like receptor 4 signaling in human macrophages. FASEB J. 26, 2019‐2030 (2012). www.fasebj.org

Reactive oxygen species damage various cell components including DNA, proteins, and lipids, and these impairments could be a reason for severe human diseases including atherosclerosis. Forkhead box O1 (FOXO1), an important metabolic transcription factor, upregulates antioxidant and proapoptotic genes during oxidative stress. Apolipoprotein A-I (ApoA-I) forms high density lipoprotein (HDL) particles that are responsible for cholesterol transfer from peripheral tissues to liver for removal in bile in vertebrates. The main sources for plasma ApoA-I in mammals are liver and jejunum. Hepatic apoA-I transcription depends on a multitude of metabolic transcription factors. We demonstrate that ApoA-I synthesis and secretion are decreased during H₂O₂-induced oxidative stress in human hepatoma cell line HepG2. Here, we first show that FOXO1 binds to site B of apoA-I hepatic enhancer and downregulates apoA-I gene activity in HepG2 cells. Moreover, FOXO1 and LXRα transcription factors participate in H₂O₂-triggered downregulation of apoA-I gene together with Src, JNK, p38, and AMPK kinase cascades. Mutations of sites B or C as well as the administration of siRNAs against FOXO1 or LXRα to HepG2 cells abolished the hydrogen peroxide-mediated suppression of apoA-I gene.

Dysregulation of adipose tissue functions makes a significant contribution to the pathogenesis of metabolic syndrome, one of the most common diseases in recent years. Adipose tissue is an organ that secretes at least several dozen signaling molecules, adipokines. One of the most studied and at the same time mysterious adipokines is adiponectin. The latter is due to the lack of clear ideas about the biological role of this adipokine, the presence of its several molecular forms with different activity and several types of receptors to this adipokine localized in almost all cells of the body. The purpose of this review is to summarize and analyze the available information about the molecular mechanisms of the effect of adiponectin on metabolism of carbohydrates, lipids and lipoproteins. The literature search was conducted by the keywords "adiponectin" and "metabolic syndrome" in the Pubmed and Elibrary.ru databases for the period from 1995 to 2021.According to the results of the literature analysis, it is assumed that adiponectin is involved in energy metabolism as a «satiety» hormone that promotes the utilization and storage of energy-rich substrates, fatty acids and glucose, which prevents the development or mitigates the already developed insulin resistance. This reduces the amount of plasma triglycerides and increases the level of high-density lipoproteins in the plasma. Adiponectin affects metabolic processes by activating the AdipoR1-APPL1-LKB1-AMPK, AdipoR1-APPL1-p38, AdipoR2-PPARa cascades, and possibly by activating the ceramidase and phosphoinositide pathways and insulin signaling. In addition to the AdipoR1/2 receptors, the adhesion molecule T-cadherin may be involved in the transduction of the adiponectin signal in endothelial and muscle cells. The mechanisms of signal transduction from T-cadherin, as well as from AdipoR2, remain unclear. Studies on the mechanisms of the action of individual molecular forms of adiponectin are extremely rare. The analysis shows the complex nature of adiponectin signaling, many of the mechanisms of which remain undiscovered, and it is possible that the near future will bring us significant progress in this area.