Abstract
Recently, pharmacological activation of brown fat and induction of white fat browning (beiging) have been considered promising strategies to treat obesity. To search for natural products that could stimulate the process of browning in adipocytes, we evaluated the activity of trans-cinnamic acid (tCA), a class of cinnamon from the bark of Cinnamomum cassia, by determining genetic expression using real time reverse transcription polymerase chain reaction (RT-PCR) and protein expression by immunoblot analysis for thermogenic and fat metabolizing markers. In our study tCA induced brown like-phenotype in 3T3-L1 white adipocytes and activated HIB1B brown adipocytes. tCA increased protein content of brown-fat-specific markers (UCP1, PRDM16, and PGC-1α) and expression levels of beige-fat-specific genes (Cd137, Cidea, Cited1, Tbx1, and Tmen26) in 3T3-L1 white adipocytes, as well as brown-fat-specific genes (Lhx8, Ppargc1, Prdm16, Ucp1, and Zic1) in HIB1B brown adipocytes. Furthermore, tCA reduced expression of key adipogenic transcription factors C/EBPα and PPARγ in white adipocytes, but enhanced their expressions in brown adipocytes. In addition, tCA upregulates lipid catabolism. Moreover, mechanistic study revealed that tCA induced browning in white adipocytes by activating the β3-AR and AMPK signaling pathways. tCA can induce browning, increase fat oxidation, reduce adipogenesis and lipogenesis in 3T3-L1 adipocytes, and activate HIB1B adipocytes, suggesting its potential to treat obesity.
Highlights
Obesity is associated with numerous other metabolic complications including diabetes, hypertension, hyperlipidemia, atherosclerosis, and cardiovascular diseases [1]
There are three types of fat in humans: (1) white adipose tissue (WAT), which makes up most fat in adults; (2) brown adipose tissue (BAT), which is involved in energy expenditure; and (3) brown in white fat, which converts from white adipocytes to brown-like adipocytes and contributes to energy expenditure in humans [4]
Our results demonstrated that trans-cinnamic acid (tCA) strikingly activated HIB1B brown adipocytes by enhancing enhancing expression levels of brown fat-specific proteins
Summary
Obesity is associated with numerous other metabolic complications including diabetes, hypertension, hyperlipidemia, atherosclerosis, and cardiovascular diseases [1]. Nutrients 2019, 11, 577 studies have identified ectopic expression of other hallmark proteins, such as PGC-1α and PRDM16, as novel beige-fat-specific markers [13,14]. Among several analogs of cinnamon, trans-cinnamic acid (tCA) is known to exhibit various health-promoting properties, including anti-diabetic [26], anti-inflammatory, and anti-cancer activities [27]. Another important feature displayed by tCA is that it can reduce body weight of obese rats [28] by improving insulin sensitivity and blood lipids [29]. The objective of the present study was to examine physiological roles of tCA in lipid metabolism of 3T3-L1 white adipocytes and HIB1B brown adipocytes, focusing on browning
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