Table 5.

Effect of curcumin on obesity in cell, animal, and human

First author, yr [ref]	Experimental design and treatments	Results
In vitro study
Ahn, 2010 [134]	3T3-L1 cells treated with CUR (0, 10 and 25 µM) for 48 hours.	↓ Adipocyte differentiation and lipid accumulation ↓ C/EBPα and PPARγ, SREBP-1 and FASN ↓ MAPK phosphorylation ↑ β-catenin translocation ↑ Wnt signaling
Dong, 2011 [135]	Rabbit subcutaneous adipocytes treated with CUR (0–20 µg/mL) for 24 hours.	↑ Cholesterol efflux from adipocytes ↑ PPARγ, LXRα, ABCA1
Ejaz, 2009 [136]	3T3-L1 cells treated with CUR (0, 5,10 and 20 µM) for 24 hours.	↓ Adipocyte differentiation, fat accumulation, and adipogenesis ↑ CPT-1 and fat oxidation ↓ ACC, GPAT-1 ↑ AMPK activation ↑ Apoptosis
Gonzales, 2008 [137]	3T3-L1 cells treated with CUR (0–20 µM) for 24 or 62 hours.	↓NF-κB level and nuclear translocation ↓ Expression of IL-6, TNF-a and COX2
Kim, 2011 [138]	3T3-L1 cells treated with CUR (0–30 µM) for 18 hours, 24 hours, 48 hours, and 6 days.	↓ Adipocyte differentiation and fat accumulation ↓ Cell viability ↓ MCE process ↓ C/EBPβ, PPARγ and C/EBPα
Lee, 2009 [139]	3T3-L1 cells treated with CUR (0–50 µM) for 8 days.	↑ AMPK ↓ PPARγ ↑ Phosphorylation of ACC ↓ Fat accumulation
Shao, 2012 [140]	Primary cell culture from epididymal fat pads treated with CUR (0–20 µM) for 0–60 minutes.	↔ Wnt signaling ↓ Inflammatory and oxidative pathway ↑ Insulin-stimulated PKB phosphorylation ↓NF-κB signaling
Wang, 2009 [141]	3T3-L1 cells treated with CUR (0–20 µM) for 24 or 48 hours.	↑ Insulin-stimulated glucose uptake ↓ TNF-α and IL-6, NF-κB p65 ↓ JNK, ERK1/2, p38MAPK
Woo, 2007 [142]	Raw 264.7 (murine macrophage cell line) and 3T3-L1 cells treated with CUR (0.1, 1, 10 µM) for 24 hours.	↓ Migration of macrophages ↓ Nitric oxide ↓ MCP-1 and TNF-α
Xie, 2012 [143]	3T3-L1 cells treated with CUR (0–30 µM) for 2 and 24 hours.	↑ Apoptosis at 30 µM ↓ Glycerol release ↓ MAPK phosphorylation ↓ HSL recovered
Zhao, 2011 [144]	3T3-L1 cells treated with CUR (0–100 µM) for 0–8 days.	↓ Adipocyte differentiation and lipid accumulation ↓ FAS, PPARγ, CD36
Animal
Asai, 1999 [153]	ddY mice (9-week-old). Groups including control group or turmeric group (>99% curcuminoid) group for 1 week.	↓ TAG and cholesterol levels in liver ↓ α-tocopherol levels in RBC ↓ Lipid peroxidation (↓TBARS in liver and ↓ PLOOH in RBC)
Asai, 2001 [147]	Male Sprague-Dawley rats (7-week-old) in a HF diet-induced obesity model. Groups including HF group, HF+0.2%CUR group (w/w curcuminoids in diet), or HF+1%CUR group for 2 weeks.	In HF+1%CUR group: ↓ Epididymal adipose tissue weight ↓ Liver TAG and cholesterol ↓ Plasma TAG in the VLDL fraction ↑ Hepatic acyl-CoA oxidase activity
Ejaz, 2009 [136]	Male C57BL/6 mice (4-week-old) in a HF diet-induced obesity model. Groups including control group, HF group, or HF+CUR group (500 mg/kg of diet) for 12 weeks.	↓ BW, fat, microvessel density in adipose tissue. ↓ Liver weights and hepatic steatosis ↓ Serum glucose and total cholesterol ↓ Angiogenesis (↓ VEGF and VEGFR-2 mRNA) ↑ Fatty acid and energy metabolism (↑ P-AMPK, P-ACC, and CPT-1 mRNA expression; ↓ GPAT-1, PPARγ and C/EBPα mRNA expression)
He, 2012 [151]	Male C57BL/6J mice (8-week-old) in a HF diet-induced obesity and insulin resistance model. Groups including LF group, HF group, and HF+CUR (50 mg/kg BW by gavage) for 15 days.	↔ BW ↑ Glucose disposal and insulin sensitivity (↓ insulin, HMOA-IR) ↓ Oxidative stress (↓ MDA and ROS in skeletal muscle and mitochondria) ↑ NrF2 signaling in skeletal muscle)
Jang, 2008 [154]	Male Golden-Syrian hamsters (4-week-old) in a HF diet-induced obesity model. Groups including HF group or HF+CUR (0.05% in diet) for 10 weeks.	↔ BW, food intake, fat pad mass, plasma glucose ↓ Plasma FFA, total cholesterol, TG, leptin, insulin, HOMA-IR ↑ Plasma HDL-C, apo A-I, PON ↓ Hepatic cholesterol and TG ↑ FA β-oxidation activity ↓ FAS, HMG-CoA reductase, ACAT activities ↓ Lipid peroxide levels (↓ RBC and hepatic TBARS)
Kempaiah, 2006 [155]	Female Wistar rats in a cholesterol-rich diet. Groups including cholesterol control group or cholesterol+0.2%CUR (w/w in diet) group for 8 weeks.	↓ Activity of Ca2+, Mg2+-ATPase in RBC membranes
Leray, 2011 [156]	European obese cats (6.5-year-old). Groups including control group, citrus group, or CUR group (0.09%) for 8 weeks.	↓ Plasma AGP concentration ↓IFN-γ and IL-2 mRNA levels ↔ mRNA expression of TNF-α, IL-1β, IL-4, IL-5, IL-10, IL-12, IL-18, TGF-β
Mesa, 2003 [157]	Male New Zealand rabbits in a cholesterol-rich diet. Groups including cholesterol control group or cholesterol+turmeric group (1.66 mg/kg BW) for 10 days and 30 days.	↓ Lipid peroxidation (↓ TBARS in RBC membranes, ↓ H2O2 and TBARS in liver microsomes)
Oner-Iyidogan, 2013 [148]	Male Sprague-Dawley rats in a HF diet-induced obesity model. Groups including control group, CUR100 group (100 mg/kg/BW/d), CUR400 group (400 mg/kg/BW/d), HF group, HF+CUR100, or HF+CUR400 for 8 weeks.	↓ Liver TG ↓ Serum fetuin-A
Pongchaidecha, 2009 [146]	Male Wistar rats (100–120 g) in a HF diet-induced obesity model. Groups including control group, HF control group, HF+30mg/kg BW curcuminoid group, HF+60 mg/kg BW curcuminoid group, or HF+90mg/kg BW curcuminoid group for 12 weeks.	↓ Plasma FFA and glucose levels ↔ Insulin, HOMA-IR Improved cardiac autonomic disturbance
Rao, 1970 [145]	Female Wistar rats (45-day-old) in a cholesterol-rich diet. Groups including control group, 0.5% (w/w in diet) CUR group, cholesterol group, cholesterol+0.1%CUR group, cholesterol+0.25%CUR group, or cholesterol+0.5%CUR group for 7 weeks.	In cholesterol-supplemented groups: ↓ Liver weight ↓ Free cholesterol and cholesterol levels in serum and liver ↑ Cholic acid, deoxycholic acid, and free cholesterol excretion in feces ↓ β-lipoprotein and ↑ α-lipoprotein in serum
Shao, 2012 [140]	Male C57BL/6J mice (5-week-old) in a HF diet induced-obesity model. Groups including LF group, HF group, or HF+CUR (4 g/kg diet, added 2 days/week) group for 28 weeks.	↓ BW and fat ↓ Hepatic lipogenic gene expression (↓ NF-κB, SREBP-1c, ChREBP and LPK) ↑ Glucose disposal and insulin sensitivity ↔ Wnt signaling in mature adipocytes ↓ Inflammatory and oxidative pathway in adipocytes
Weisberg, 2008 [149]	Male wild-type C57BL/6J mice (8-10-week-old) in a diet-induced-obesity (DIO) model. Male ob/ob C57BL/6J mice (3-5-week-old). At age of 20 weeks, groups including DIO control group, DIO+3%CUR (w/w in diet), ob/ob control group, or ob/ob+3%CUR for 60 days.	↓ BW and body fat ↑ Glycemic status and insulin sensitivity ↑ ER stress response (↑ mRNA expression of SIRT1, HSP70, HSP90, FOXO1α in white adipose tissue) ↓ Adipose, hepatic, and systemic inflammation (↓ MCP-1) ↑ mRNA expression of adiponectin ↓ Hepatic NF-κB activity
Yekollu, 2011 [152]	Male C57BL/6J, ob/ob mice and nonobese littermates in a model of steatosis. Groups including ob/ob control group, lipo group, ob/ob+CUR group, nonobese control group, or nonobese+CUR group for 24 or 72 hours.	↓NF-κB pathway ↓ Proinflammatory cytokine (↓ TNF, IL-6; ↑ IL-4) ↑ Insulin sensitivity (↓ fasting glucose and insulin, HOMA-IR) ↑ Serum adiponectin
Yu, 2008 [150]	Male Sprague-Dawley rats in a HF diet-induced obesity model. Groups including control group, highCUR (5.00 g/kg BW, HF group, HF+lowCUR (1.25 g/kg diet) group, or HF+highCUR (5.00 g/kg diet) for 4 weeks.	↓ BW, blood glucose, insulin, leptin, TNF-α ↓ Insulin resistance and leptin resistance
Human
Baum, 2007 [160]	Randomized, double-blinded, placebo-controlled trial. Elderly (n=36, > 50 y) in Hong Kong. Groups including placebo group, 1 g/d CUR group, or 4 g/d CUR group for 6 months.	↔ Serum lipid profile (TAG, total, LDL-C, HDL-C)
Ramirez-Bosca, 2000 [158]	A pre-post study. Healthy adults (n=8, 43–70 yr) in Spain. All subjects received oral administration of CUR (10 mg/d) for 30 days.	↓ Serum LDL, apo B, apo B/apo A ↑ Serum HDL and apo A
Ramirez-Bosca, 2000 [159]	A pre-post study. Healthy adults (n=8, 43–70 yr) in Spain. All subjects received oral administration of CUR (10 mg/d, twice a day) for 15 days.	↓ Plasma fibringen

Abbreviations: ABCA1, ATP binding cassette transporter A1; ACAT, Acyl CoA:cholesterol acyltransferase; ACC, acetyl-Coenzyme A carboxylase; AGP, a1-acid glycoprotein; AMPK, AMP-activated protein kinase; BW, body weight; Ca, calcium; C/EBP, CCAAT/enhancer-binding protein; ChREBP, carbohydrate-responsive-element-binding protein; CPT-1, Carnitine palmitoyltransferase-1; COX2, cyclooxygenase 2; CUR, curcumin; ER, endoplasmic reticulum; ERK1/2, extracellular signal-regulated protein kinases 1 and 2; FA, fatty acids; FASN (FAS), fatty acid synthase; FFA, free fatty acid; FOXO1, forkhead box protein O1; GPAT-1, glycerol-3-phosphate acyl transferase-1; HDL-C, high density lipoprotein-cholesterol; HF, high fat; HMG-CoA, 3-hydroxy-3-methyl-glutaryl-CoA; HOMA-IR, homeostasis model assessment-insulin resistance; HSL, hormone sensitive lipase; HSP, heat shock protein; IFN, interferon; IL, interleukin; JNK, Jun NH2-terminal kinase; LDL-C, low density lipoprotein-cholesterol; LPK; liver-type pyruvate kinase; LXR, liver X receptor; MAPK, mitogen-activated protein kinase; MCE, mitotic clonal expansion; MCP-1, monocyte chemoattractant protein-1; MDA, malondialdehyde; Mg, magnesium; NF-kB, nuclear factor kappa B; Nrf2: nuclear factor erythroid-2-related factor-2; PKB, protein kinase B; PLOOH, phospholipid hydroperoxides; PON, paraoxonase; PPAR, peroxisome proliferators-activated receptor; RBC, red blood cell; ROS, reactive oxygen species; SIRT1, sirtuin (silent mating type information regulation 2 homolog) 1; SREBP-1, sterol regulatory element-binding protein-1; TAG, triacylglycerol; TBARS, thiobarbituric acid reactive substances; TG, triglyceride; TGF-β, transforming growth factor- β; TNF-α, tumor necrosis factor alpha; VEGF, vascular endothelial growth factor; VEGFR-2, vascular endothelial growth factor-receptor 2; VLDL, very low density lipoprotein; ↑, increase; ↓, decrease; ↔, no change.