3.1.3 Promoting BAT activity and WAT browning
Adipose tissue is critical in regulating insulin sensitivity due to its lipid storage capacity, thermogenic function, and endocrine regulation capacity. Generally, adipose tissue can be roughly classified into three types: WAT, brown adipose tissue (BAT), beige adipose tissue. WAT is mostly located in the subcutaneous and visceral/omental regions and is used for lipid storage. BAT plays a significant role in energy expenditure and is primarily found in the interscapular space, supraclavicular regions, paravertebral and perirenal areas. Beige adipose tissue is defined as a transitional adipose tissue, which has properties of both WAT and BAT (Gustafson, Hedjazifar, Gogg, Hammarstedt & Smith, 2015).
Brown adipocytes have small lipid droplets, great mitochondrial number, brown exterior, and excellent capacity in energy expenditure. BAT generates heat by absorbing fatty acid from the circulation and uncoupling chemical energy production (such as ATP) via oxidative phosphorylation into non-shivering thermogenesis, leading to ectopic lipid accumulation. BAT activation also plays a critical role in glycemic control by increasing systemic glucose disposal (Chait & den Hartigh, 2020; Chondronikola et al., 2014). Numerous variables, including as cold stimulation, gut microbiota composition, PFG-1α, PPARγ, SIRT1 expression and β3 adrenergic receptor (β3-AR), contribute to WAT browning (Li et al., 2017; Ma et al., 2022). It was established that BAT transplantation potently alleviated IR in a dose-dependent manner on the BAT-recipient mice (Stanford et al., 2013). When exposed to cold, BAT-positive men could increase resting energy expenditure, glucose oxidation, whole-body glucose disposal and insulin sensitivity (Chondronikolaet al., 2014). Besides, BAT might have a greater impact on women than on males (Keuper & Jastroch, 2021). Thus, it might be a feasible way to improve IR and T2DM by promoting BAT activity and WAT browning.
Allicin, an organic sulfur compound rich in Allium sativum L., is a potential medicine for the treatment of obesity and other metabolic diseases. Allicin addition increased expression of brown adipocyte-specific genes (such as UCP1) by activating ERK1/2 and Krüppel-like factors 15 (KFL-15), thus inducing the formation of brown-like adipocytes in differentiated 3T3-L1 and inguinal WAT in mice and accelerating lipid oxidation and energy expenditure (Lee, Rhee, Kim, Um & Pyo, 2019).
Diphyllin is a common aryl naphthalene lignan. Duan et al. found that diphyllin intervention improved the glucolipid metabolism and insulin sensitivity, as evidenced by the increased thermogenesis in BAT and beige adipose tissues, as well as the enhanced BAT generation and WAT browning. It was speculated that diphyllin acted through inhibiting V-ATPase and intracellular autophagy (Duan et al., 2020). Besides, it is worth mentioning that aryl naphthalene lignans are widely found in various dietary or medicinal plants and have multiple biological activities. For example, some of them were used as folk medicine for adjuvant therapy of DM (Jin et al., 2010; Sun et al., 2016).