The Role of Adipose Tissue Lipolysis in Diet-Induced Obesity: Focus on Vimentin

Abstract

Corresponding author: Hye Jin Yoo https://orcid.org/0000-0003-0600-0266 Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, 148 Gurodong-ro, Gurogu, Seoul 08308, Korea E-mail: [email protected] Adipose tissue (AT) is the main organ for energy storage. During periods of energy demands, such as fasting and physical exercise, fatty acids (FAs) can be mobilized from fat stores to meet energy needs. Lipolysis is the catabolic pathway through which stored triglycerides (TGs) are hydrolyzed into FA and glycerol. Three lipases work sequentially [1]. First, adipose triglyceride lipase (ATGL) hydrolyzes TG into diacylglycerol (DAG) and FA. Then, hormone-sensitive lipase (HSL) cleaves DAG into monoacylglycerol, which is ultimately converted into FA and glycerol by monoacylglycerol lipase. HSL resides freely in the cytosol and can associate with lipid droplets. Lipolytic hormones such as catecholamines stimulate lipolysis primarily via cyclic adenosine monophosphate (cAMP)-mediated activation of protein kinase A (PKA) [2]. PKA then phosphorylates HSL serine residues 563, 659, and 660, leading to translocation of HSL to a lipid droplet and to its active participation in lipolysis [3]. On the other hand, AMP-activated protein kinase (AMPK) phosphorylates HSL Ser565 and prevents PKA-mediated phosphorylation of this enzyme [3]. In addition to the cAMP/PKA signaling cascade, pathways involving cGMP-dependent protein kinase, protein kinase C (PKC), and extracellular signal-regulated kinase (ERK) contribute to activate lipolysis in adipocytes [4]. During the development of obesity, AT expands tremendously and adipocyte size increases to neutralize and store nutritional overload [5]. This process is necessary to protect the body from peripheral insulin resistance. However, when the adipocytes are eventually unable to store excess lipids, two important pathological processes in AT are important for the development of metabolic diseases: AT inflammation and hypertrophy [5]. In obese individuals, AT inflammation due to the recruitment of T-cells and macrophages has been shown to contribute to insulin resistance by disturbed adipokine balance [6,7]. Moreover, large adipocytes increase lipolysis and promote elevated circulating TGs, non-esterified fatty acids (NEFAs) and glycerols. This process is accompanied by redirection of FA to the liver, promoting hepatic TG accumulation [8]. Vimentin is a type III intermediate filament that comprises a type of cytoskeletal element [9]. It is expressed in mesenchymal cells, including adipocytes where it forms lipid droplets, stabilizes TG [10], and participates insulin-dependent translocation of glucose transporter type 4 (GLUT4), the predominant insulin-responsive glucose transporter isoform, to the plasma membrane [11]. Using a proteomics approach, vimentin has been considered to participate in lipolysis through direct interactions with HSL [10], in addition to its interaction with β-adrenergic receptors and ERK signaling [12]. A recent study showed that mice lacking vimentin (Vim) had less fat accumulation compared with wild-type mice, suggesting that vimentin is important for normal fat accumulation in the body [13]. However, there have been no animal studies that verified the role of vimentin in diet-induced obesity and type 2 diabetes mellitus. In the article titled, “Vimentin deficiency prevents high-fat diet-induced obesity and insulin resistance in mice,” Kim et al. [14] investigated whether vimentin deficiency affected high-fat Editorial