| 1. |
- Baboota, Ritesh, et al.
(författare)
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Emerging Role of Bone Morphogenetic Protein 4 in Metabolic Disorders
- 2021
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 70:2, s. 303-312
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Tidskriftsartikel (refereegranskat)abstract
- Bone morphogenetic proteins (BMPs) are a group of signaling molecules that belong to the TGF-beta superfamily. Initially discovered for their ability to induce bone formation, BMPs are known to play a diverse and critical array of biological roles. We here focus on recent evidence showing that BMP4 is an important regulator of white/beige adipogenic differentiation with important consequences for thermogenesis, energy homeostasis, and development of obesity in vivo. BMP4 is highly expressed in, and released by, human adipose tissue, and serum levels are increased in obesity. Recent studies have now shown BMP4 to play an important role not only for white/beige/brown adipocyte differentiation and thermogenesis but also in regulating systemic glucose homeostasis and insulin sensitivity. It also has important suppressive effects on hepatic glucose production and lipid metabolism. Cellular BMP4 signaling/action is regulated by both ambient cell/systemic levels and several endogenous and systemic BMP antagonists. Reduced BMP4 signaling/action can contribute to the development of obesity, insulin resistance, and associated metabolic disorders. In this article, we summarize the pleiotropic functions of BMP4 in the pathophysiology of these diseases and also consider the therapeutic implications of targeting BMP4 in the prevention/treatment of obesity and its associated complications.
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| 2. |
- Jersin, R. A., et al.
(författare)
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Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity, and Insulin Resistance
- 2021
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 70:3, s. 680-695
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Tidskriftsartikel (refereegranskat)abstract
- Elucidation of mechanisms that govern lipid storage, oxidative stress, and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter-1 (ASC-1), shows strong inverse correlates with visceral adiposity, insulin resistance, and adipocyte hypertrophy across multiple cohorts. Concordantly, loss of Slc7a10 function in zebrafish in vivo accelerates diet-induced body weight gain and adipocyte enlargement. Mechanistically, SLC7A10 inhibition in human and murine adipocytes decreases adipocyte serine uptake and total glutathione levels and promotes reactive oxygen species (ROS) generation. Conversely, SLC7A10 overexpression decreases ROS generation and increases mitochondrial respiratory capacity. RNA sequencing revealed consistent changes in gene expression between human adipocytes and zebrafish visceral adipose tissue following loss of SLC7A10, e.g., upregulation of SCD (lipid storage) and downregulation of CPT1A (lipid oxidation). Interestingly, ROS scavenger reduced lipid accumulation and attenuated the lipid-storing effect of SLC7A10 inhibition. These data uncover adipocyte SLC7A10 as a novel important regulator of adipocyte resilience to nutrient and oxidative stress, in part by enhancing glutathione levels and mitochondrial respiration, conducive to decreased ROS generation, lipid accumulation, adipocyte hypertrophy, insulin resistance, and type 2 diabetes.
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