Table 1.

Phytochemicals targeting specific signaling pathway act against obesity and related symptoms.

Phytochemicals	Target molecular	Major results	References
Curcumin	TLR4↓	- Anti-inflammation (↓macrophage infiltration of adipose tissue) and insulin sensitizer (↓serum glucose in GTT) in HFD-mice (0.4% of diet, 14 weeks)	(34)
Kaempferide	TLR4↓	- Anti-obesity, anti-hyperlipidemia, anti-hyperglycemia, anti-inflammation and anti-oxidation (↓body weight, ↓serum TG, TC, HDL-C, LDL-C, glucose, TNFa, MCP-1; ↑serum adiponectin; ↑liver GSH, SOD, CAT, T-AOC, GSH-Px; ↓liver MDA) in HFD-mice (10 mg/kg bw, p.o., 8 weeks).	(30)
Withaferin A	TLR4↓	- Anti-obesity, insulin sensitizer, anti-inflammation and anti-oxidation (↓body weight;↓epididymal WAT weight;↑serum adiponectin, ↓serum leptin, TC, TG, FFA, ALT, AST; ↓serum glucose in GTT and ITT; ↓serum IL-6, TNFa, IL-1b, CRP, MCP-1; ↑liver GSH, SOD, CAT, T-AOC, GSH-Px; ↓liver TBARS) in HFD-mice (1.25 mg/kg bw, p.o., 12 weeks).	(29)
Isoliquiritigenin	TLR4↓	- Attenuated adipose tissue inflammation in a co-culture model composed of adipocytes and macrophages (↓NF-kB activation, Akt phosphorylation). - Attenuated adipose tissue fibrosis in HFD-induced obese mice (↓ fibrotic area of eWAT).	(31)
Amorfrutin A1	PPARγ–agonist (AG)	- Anti-hyperglycemia and insulin sensitizer (↓body weight; ↓blood glucose; ↓HOMA-IR, ↓blood glucose and insulin in GTT; ↑pancreatic insulin; ↓plasma ALT,TG, FFA) in HFD-obese mice, and ↓ plasma insulin; ↓plasma TG; ↑pancreatic insulin in db/db mice (100 mg/ kg bw, p.o., 3 weeks). - Anti-steatosis (↓body weight; ↓plasma insulin, leptin; ↓liver TG) in HFD-obese mice (37 mg/ kg bw, p.o., 15 weeks).	(66)
Amorfrutin B	PPARα–AG PPARδ–AG PPARγ–AG	- Anti-hyperglycemia, insulin sensitizer (↓blood glucose, ↓plasma insulin, ↓HOMA-IR index, ↓blood glucose and insulin in GTT; ↓plasma TG and NEFA) in HFD-diabetic mice (100 mg/kg bw, p.o., 27 days).	(179)
Soy isoflavones	PPARα–AG PPARα–AG	- Anti-hyperlipidemia (↓liver weight, ↓liver cholesterol, ↓liver TG, ↓plasma cholesterol). - Insulin sensitizer (↓plasma insulin (male), ↓serum glucose in GTT) in obese Zucker rats (0.75 g/kg of diet, 11 weeks).	(180)
Linalool	PPARα–AG	- Anti-hyperlipidemia (↓plasma TG) in Western-diet fed C57BL6J and apoE2 mice but not in PPARα -deficient mice (100 mg/kg bw, p.o., 3 weeks).	(43)
Tyrosol	PPARα–AG	- Anti-obesity (↓body weight, ↓liver weight, ↓plasma TG, TC, and glucose) in obese mice (0.2% of diet, 16 weeks).
Ursolic acid	PPARα–AG	- Anti-hyperlipidemia (↓TG and TC content) in HepG2 cells (5–100 mM).	(79)
Picrasidine C	PPARα–AG	- Promoted PPARα transcriptional activity and induced the expression of CPT-1, PPARα, PDK4, and ABCA1 in HepG2 cells (1–20 μM).	(80)
Vaticanol C (resveratrol tetramer)	PPARα and PPARβ/δ–AG	- Activated PPARα and β/δ in bovine arterial endothelial cells (1.25–10 μM). - Upregulated hepatic expression of PPARα-responsive genes and muscle PPARβ/δ-responsive genes in wild-type, but not PPARα-knockout mice in HFD-fed mice (0.04% of diet, 8 weeks).).	(97)
Resveratrol	PPARα and PPARδ–AG	- Anti-inflammation (↓ROS, ↓IL-8) in retinal pigment epithelium cells (25 μM).	(98)
Honokiol	PPARγ–AG	- Induced glucose uptake but not adipogenesis in 3T3-L1 cells (1–10 μM). - Decreased blood glucose levels in diabetic KKAy mice with simultaneous suppression of weight gain.	(181)
Glucoraphanin	Nrf2↑	- Anti-obesity, anti-hepatic steatosis, insulin sensitizer (↓body weight; ↓fat mass;↑energy expenditure; ↓liver weight, TG, FFA, AST, ALT; ↓serum glucose in GTT and ITT; ↓HOMA-IR index) in HFD-fed wild-type mice but not in HFD-fed Nrf2 knockout mice (0.3% of diet, 14 weeks).	(126)
Sesamol	Nrf2↑	- Anti-obesity (↓body weight, eWAT, iWAT; ↓serum ALT, glucose, FFA, LDL-C; ↑energy expenditure) in HFD-mice (100, 200 mg/kg bw, p.o., 12 weeks). - Stimulated expression of UCP1 in wild-type adipocyte but not in Nrf2 knockout cells.	(127)
Curcumin	Nrf2↑	- Anti-oxidation (↓serum MDA; ↓mitochondria MDA; ↓muscle MDA, ROS); Insulin sensitizer (↓serum glucose in GTT and ITT; ↓HOMA-IR index) in HFD-mice (50 mg/kg bw, p.o., 18 weeks).	(128)
Garcinia cambogia	Nrf2↑	- Anti-hepatic steatosis, anti-hepatic apoptosis (↓serum ALT, AST, TG, TC) in HFD-mice (200, 400 mg/kg bw, p.o., 8 weeks). - Reduced lipid accumulation, apoptosis, ROS level in FFA-induced HepG2 cells (20–80 ug/ml, 24 h).	(129)
Timosaponin	Nrf2↑	- Anti-oxidation (↓serum MDA; ↑serum T-AOC, GSH-Px; ↓liver ROS, MDA; ↑liver GSH-Px; - Anti-obesity (↓body weight, epididymal and retroperitoneal fat weight, number of adipocytes in epididymal and retroperitoneal fat) in HFD-mice (0.1, 0.4 g/kg bw, p.o., 11 weeks).	(130)
EGCG	FTO↓	- Anti-adipogenesis (↓adipocyte differentiation, lipid accumulation) in 3T3-L1 cells (50–200 μM, 30 h).	(149)
Clausine E	FTO↓	- Inhibition of FTO activity in-vitro.	(182)
Garcinia cambogia	FTO	- Anti-obesity (↓body weight, fat mass, visceral fat; ↓serum TC, TG, glucose; ↑basal metabolic rate) in obese humans (214 participants, 1,000 mg/day, 6 months), the presence of polymorphisms FTO might hamper these beneficial effects.	(155)
Angelica sinensis	FTO↑	- Anti-obesity [↓body weight (10 g/kg bw)] and promoted methylation of CpG island in the FTO promoter in HFD-mice (2, 5, 10 g/kg bw, p.o., 4 weeks). - FTO expression in high dose group (10 g/kg bw) were significantly higher than control.	(153)
EGCG	↓miR-33a and miR-122	- Increase ABCA1 mRNA and protein level, not altered FAS mRNA, slightly decreased FAS protein level in HepG2 cells (50 μM).	(171)
Resveratrol	↑miR-33a and miR-122	- Increased ABCA1 protein level, and increased FAS mRNA and protein in HepG2 cells (50 μM).	(171)
Zerumbone	↓miR-146b	- Anti-obesity, insulin sensitizer (↓body weight; ↓eWAT; ↓adipocyte size; ↓serum triglyceride; ↓serum insulin; ↓glucose; ↓HOMA-IR) (0.01%, 0.025% of diet, 8 weeks). - Anti adipogenesis in 3T3-L1 cells (↓C/EBPα, PPARγ, FASN, Ap2) (5, 10 μM for 48 h).	(173)
Fisetin	↓miR-378	- Anti-hepatosteatosis (↓body weight; ↓serum cholesterol and triglyceride; ↓fat accumulation and triglyceride levels of liver in HFD-feed mice (0.5% of diet, 10 weeks).	(174)
Polyphenols extracted from Hibiscus sabdariffa	↓miR-103 and miR-107	- Anti-obesity, anti-hepatic steatosis, insulin sensitizer (↓body weight; ↓adipocyte size of eWAT; ↓serum insulin, glucose, HOMA-IR) in HFHC-feed mice.	(175)

↑, increased; ↓, decreased.