Pharmacological effects of lipid-lowering drugs on circulating adipokines

Table 2 Effects of fibrates on circulating adipokines

Subjects	Treatment	Effects on circulating adipokines	Ref.
Male Wistar rats on standard diet or HFDd	28 d of 75 mg/kg per day gemfibrozil	Leptin decreased in rats on HFDd (P < 0.01). No change in leptin in rats on standard diet.	[32]
Wistar rats on high-fat, high-glucose diet	8 wk of fenofibrate (50 mg/kg/d)	Fenofibrate reduced plasma leptin levels; no effect on plasma adiponectin. Fenofibrate reduced leptin mRNA levels; and increased adiponectin mRNA levels in epididymal fat	[33]
Rats	14 d of clofibrate	No effect on leptin mRNA levels in brown or white adipose tissue	[34]
Obese humans with T2DM and hypertriglycer-idemia	3 mo of fenofibrate (250 mg/d)	Serum leptin levels decreased from 266 ± 205 to 157 ± 122 pg/mL (P = 0.003)	[35]
Humans with hypertriglycer-idemia, central obesity, other characteristics of MetS	12 wk of fenofibrate (160 mg/d)	Adiponectin increased 7.7% from 4.10 to 4.50 μg/mL	[97]
Humans with stable CADb, hypercholester-olemia and hypertriglyceridemia	6 mo of bezafibrate (400 mg/d)	Adiponectin increased by 4 wk (P < 0.05), with further increases by 6 mo (P < 0.01). Bezafibrate reduced TNF-α	[80]
Nondiabetic men with insulin resistance and dyslipidemia; Male sprague-dawley rats on HFD; 3T3-L1 adipocytes	8 wk of fenofibrate (200 mg/d) in humans. 2 wk of fenofibrate (200 mg/kg per day) in rats. 24 h of fenofibrate (10, 50, 100 μmol/L) in 3T3-L1 adipocytes.	Fenofibrate decreased serum RBP4 (34.8 ± 4.0 to 24.4 ± 2.1 μg/mL) and increased adiponectin (11.3 ± 6.7 to 16.5 ± 7.2 μg/mL) in humans. Fenofibrate reduced the HFD-induced increase in RBP4 in rats. Fenofibrate reduced HFD-induced increase in RBP4 mRNA in adipose tissue of rats. Fenofibrate attenuated the HFD-induced decrease in adiponectin mRNA in adipose tissue of rats. Fenofibrate suppressed RBP4 mRNA levels by 22% at highest concentration and increased adiponectin mRNA levels by 46% at highest concentration in 3T3-L1 adipocytes	[100]
Humans with MetSc	Longitudinal study over a period of ~6.2 year of 400 mg/d bezafibrate	After 2 year of treatment, adiponectin increased, with the median percentage change being +9.8% (P < 0.0001)	[98]
Humans with hypertriglyceridemia; some with MetSc	8 wk of fenofibrate (200 mg/d)	Adiponectin increased by 14% ± 5% (P = 0.008)	[99]
Men with hypertriglyceridemia	12 wk of 150 mg/d (n = 7) or 4 wk of 150 mg/d then 8 wk of 300 mg/d (n = 4) fenofibrate	HMWb adiponectin increased from 3.0 ± 1.5 to 3.4 ± 1.7 μg/mL (P < 0.05). No change in total adiponectin	[101]
Humans with T2DMa and mixed hyperlipoproteinemia	6 wk of fenofibrate (200 mg/d)	No change in adiponectin or resistin	[92]
Humans with insulin-resistant MetSc	12 wk of fenofibrate (200 mg/d)	No change in plasma leptin, adiponectin or TNF-α concentrations	[36]
Obese women with T2DMa	3 mo of fenofibrate (200 mg/d)	No effect on adiponectin or resistin	[102]
Hypercholesterolemic rabbits and adipocytes from these rabbits	4 wk of fenofibrate (30 mg/kg per day or 10-100 μmol/L)	Fenofibrate decreased high cholesterol diet-induced increases in TNF-α by 44.7%. Fenofibrate reduced TNF-α release by adipocytes (P < 0.05) compared to the high cholesterol group (10.45 ± 0.33 vs 17.23 ± 0.26 pg/mL, P < 0.05)	[123]

^aType 2 diabetes mellitus;

^bHigh molecular weight;

^cMetabolic syndrome;

^dHigh-fat diet. TNF-α: Tumor necrosis-factor-α; RBP4: Retinol binding protein 4; HMW: High-molecular weight; T2DM: Type 2 diabetes; Ref: Reference.