Abstract
The discovery of active brown adipose tissue (BAT) in adult humans and the fact that it is reduced in obese and diabetic patients have put a spotlight on this tissue as a key player in obesity-induced metabolic disorders. BAT regulates energy expenditure through thermogenesis; therefore, harnessing its thermogenic fat-burning power is an attractive therapeutic approach. We aimed to enhance BAT thermogenesis by increasing its fatty acid oxidation (FAO) rate. Thus, we expressed carnitine palmitoyltransferase 1AM (CPT1AM), a permanently active mutant form of CPT1A (the rate-limiting enzyme in FAO), in a rat brown adipocyte (rBA) cell line through adenoviral infection. We found that CPT1AM-expressing rBA have increased FAO, lipolysis, UCP1 protein levels and mitochondrial activity. Additionally, enhanced FAO reduced the palmitate-induced increase in triglyceride content and the expression of obese and inflammatory markers. Thus, CPT1AM-expressing rBA had enhanced fat-burning capacity and improved lipid-induced derangements. This indicates that CPT1AM-mediated increase in brown adipocytes FAO may be a new approach to the treatment of obesity-induced disorders.
Highlights
Obesity is a major public health problem and a worldwide epidemic contributing to the development of associated pathological conditions, such as insulin resistance, type 2 diabetes, cardiovascular disease, nonalcoholic fatty liver disease, and some forms of cancer among others [1,2]
Differentiation was evaluated by Oil Red O staining, mRNA expression of brown adipose tissue (BAT) differentiation markers, and protein levels of uncoupling protein 1 (UCP1)
The mRNA levels of the brown adipocyte differentiation markers cell death-inducing DNA fragmentation factor-α-like effector A (CIDEA), peroxisome proliferatoractivated receptor gamma coactivator 1 alpha (PGC1a), PR domain-containing 16 (PRDM16) and Zic1 increased at day 3, and peaked at day 6 of differentiation (Fig 1C)
Summary
Obesity is a major public health problem and a worldwide epidemic contributing to the development of associated pathological conditions, such as insulin resistance, type 2 diabetes, cardiovascular disease, nonalcoholic fatty liver disease, and some forms of cancer among others [1,2]. Adipose tissue has gained a crucial role in the study of the mechanisms involved in PLOS ONE | DOI:10.1371/journal.pone.0159399. CPT1 in Brown Adipocytes (CIBEROBN) (Grant CB06/03/0001 to DS), the Centro de Investigación Biomédica en red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), the Generalitat de Catalunya (2014SGR465 to DS, and 2014SGR48 to AZ), the Comunidad de Madrid (S2010/BMD-2423 to MJO and AMV), INTERREG IV-B-SUDOE-FEDER (DIOMED, SOE1/P1/E178) to AZ, and the European Foundation for the Study of Diabetes (EFSD)/ Janssen-Rising Star and L’Oréal-UNESCO “For Women in Science” research fellowships to LH. AZ is a recipient of ICREA-Academia (Generalitat de Catalunya) and MW is a recipient of the Ciência sem Fronteiras-CNPq fellowship (237976/2012-9). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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