3.1.5 Activating SIRT1
SIRT1, a member of Sirtuins, is the major nuclear NAD-dependent
deacetylase in vivo . SIRT1 is involved in the regulation of many
processes in the organism, such as mitochondrial biogenesis,
inflammation, intracellular metabolism, stress resistance, apoptosis and
glucose homeostasis (Szkudelski & Szkudelska, 2015). The mechanisms by
which SIRT1 alleviates IR include attenuating mitochondrial dysfunction
via the SIRT1–SIRT3–mitochondrial complex I pathway (Zhang et al.,
2015), inhibiting protein tyrosine phosphatase 1b (PTP1B, a negative
regulator of the insulin signaling pathway) (Sun et al., 2007),
regulating macrophages infiltration and polarization (Hui et al., 2017),
suppressing inflammatory responses in macrophages (Yoshizaki et al.,
2010). In addition, SIRT1 is connected to BAT activity and WAT browning.
In support, Xu et al. found that SIRT1 deficiency significantly promoted
BAT degeneration in HFD-challenged mice, resulting in IR aggravation (Xu
et al., 2016). Another study that
demonstrated how SIRT1 significantly increased WAT browning by
deacetylating PPAR on Lys268 and Lys293 further confirmed this finding
(Li Qiang & Yingming Zhao, 2012). In addition to PPARγ, there are
numerous additional substrates for SIRT1 deacetylation, including FOXO1,
nuclear factor kappa-B (NF-κB) P65, PGC-1α, which are all closely
associated with IR. Hence, activation of SIRT1 might be a prospective
target for selecting medicine to improve
IR.
Resveratrol (Supporting Information Table S4), a non-flavonoid
polyphenolic organic compound, is an antitoxin produced by plants being
irritated. Cote et al. demonstrated that resveratrol improved
hypothalamic insulin sensitivity by activating SIRT1 and AMPK in
duodenum to initiate a gut–brain–liver neuronal axis in rats (Cote et
al., 2015).
Berberine, a quaternary ammonium alkaloid, is a main effective
constituent of Coptis chinensis . It was evidenced that berberine
alleviated HG-induced IR by stimulating liver kinase B1/AMPK/PGC1α
pathway in the liver of mice (Li, Wang, Shen, Bai & Xu, 2020). By
targeting the MEKK1/MEK/ERK pathway, Berberine could alleviate
TNF-α-induced IR in hepatocyte (Li et al., 2022). Berberine also
potently promoted adipose tissue remodeling and thermogenesis by
regulating PPARγ deacetylation via AMPK/SIRT1 pathway (Xu et al., 2021).
Furthermore, a previous study suggested that berberine could improve
insulin signaling transduction by reducing ERS (Wang, Lu, Xu & Dong,
2010).
Patchouli alcohol, a tricyclic sesquiterpene, naturally exists inPogostemon cablin Benth. Patchouli alcohol could ameliorate
inflammation, skeletal muscle IR and hepatic steatosis, and improve
systematic glucose tolerance and insulin sensitivity in HFD-induced mice
by up-regulating fatty acid oxidation via liver kinase
B1/AMPK/SIRT1-dependent pathway (Pyun et al., 2021).