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).