Hydroxychloroquine improves high-fat-diet-induced obesity and organ dysfunction via modulation of lipid level, oxidative stress, and inflammation

Figures & data

Figure 1. Diagram of the experimental design. After a week of acclimatization, male albino rats weighing 120–150 g were fed a high-fat diet (HFD) with or without HCQ (40 mg/kg of body weight [BW]/day orally) for 16 weeks. All rats were analyzed after 18 weeks. Then, the blood and liver tissue were collected for biochemical evaluation.

Figure 2. Effect of HCQ on body weight changes (a), and weekly glucose levels (b) of the studied groups. Cont.: control, HCQ: hydroxychloroquine, HFD: high-fat diet. ** and *** indicate statistical significance at P < 0.01 and P < 0.001, respectively, compared with the control group. ## and ### indicate statistical significance at P < 0.01 and P < 0.001, respectively, compared with the HCQ group. $$$ indicates statistical significance at P < 0.001 compared with the HFD group.

Table 1. Effect of HCQ on glucose levels, glycosylated hemoglobin, and insulin sensitivity in HFD-fed rats.

	Control	HCQ	HFD	HFD + HCQ
Glucose (mg/dl)	98.8 ± 6.7	96.6 ± 5.5	430.7 ± 13.7^***, ###	146.0 ± 8.8^*, ##, $$$
HbA1c (%)	3.7 ± 0.1	3.8 ± 0.3	8.3 ± 0.2^***, ###	4.6 ± 0.2^*, $$$
Insulin (pmol/L)	29.5 ± 2.3	30.2 ± 2.1	89.4 ± 2.2^***, ###	46.4 ± 3.5^**, ##, $$$
HOMA-IR	1.0 ± 0.1	1.0 ± 0.1	13.7 ± 1.0^***, ###	2.4 ± 0.7^*, #, $$$
HOMA-β	52.3 ± 29.9	55.0 ± 30.2	12.7 ± 1.6^*, #	29.8 ± 4.9
HOMA-IS	1.0 ± 0.1	1.0 ± 0.1	0.1 ± 0.01^***, ###	0.4 ± 0.1^***, ###, $$$

HCQ: hydroxychloroquine, HFD: high-fat diet, HbA1c: hemoglobin A1c, HOMA-IR: homeostatic model assessment of insulin resistance, HOMA-β: homeostatic model assessment of β-cell function, HOMA-IS: homeostatic model assessment of insulin sensitivity.

Data are expressed as mean ± SEM (n = 5). *, **, and *** indicate statistical significance at P < 0.05, P < 0.01, and P < 0.001, respectively, compared with the control group. ^#, ^##, and ^### indicate statistical significance at P < 0.05, P < 0.01, and P < 0.001, respectively, compared with the HCQ group. ^$ indicates statistical significance at P < 0.001 compared with the HFD group.

Figure 3. Effect of HCQ on the levels of cholesterol (a), triglyceride (b), low-density lipoprotein (LDL-C) (c), very low-density lipoprotein (VLDL-C) (d), high-density lipoprotein (HDL-C) (e), and D-dimer (f) in serum of rats in different groups. Cont.: control, HCQ: hydroxychloroquine, HFD: high-fat diet. Values are expressed as means ± SEM (n = 5). (*, **, and *** indicate statistical significance at P < 0.05, P < 0.01, and P < 0.001, respectively, compared with the control group. # and ### indicate statistical significance at P < 0.05 and P < 0.001, respectively, compared with the HCQ group. $$$ indicates statistical significance at P < 0.001 compared with the HFD group).

Figure 4. Effect of HCQ on the serum level of troponin-T (a), as well as the activities of creatine kinase myocardial band (CK-MB) (b) and lactate dehydrogenase (LDH) (c) in different groups. Cont.: control, HCQ: hydroxychloroquine, HFD: high-fat diet. Values are expressed as means ± SEM (n = 5). (*, **, and *** indicate statistical significance at P < 0.05, P < 0.01, and P < 0.001, respectively, compared with the control group. # and ### indicate statistical significance at P < 0.05 and P < 0.001, respectively, compared with the HCQ group. $$$ indicates statistical significance at P < 0.001 compared with the HFD group).

Figure 5. Effect of HCQ on the oxidative stress marker 4-hydroxynonenal (4-HNE) (a), glutathione (GSH) content (b), and glutathione peroxidase (GPx) activity (c) in the liver of rats in different groups. Cont.: control, HCQ: hydroxychloroquine, HFD: high-fat diet. Values are expressed as means ± SEM (n = 5). (** and *** indicate statistical significance at P < 0.01 and P < 0.001, respectively, compared with the control group. ## and ### indicate statistical significance at P < 0.01 and P < 0.001, respectively, compared with the HCQ group. $$$ indicates statistical significance at P < 0.001 compared with the HFD group).

Figure 6. Effect of HCQ on the serum level of tumor necrosis factor alpha (TNF-α) (a), interleukin-6 (IL-6) (b), and leptin (c); interleukin-10 (IL-10) (d) and adiponectin (e) of rats in different groups. Cont.: control, HCQ: hydroxychloroquine, HFD: high-fat diet. Values are expressed as means ± SEM (n = 5). (*, **, and *** indicate statistical significance at P < 0.05, P < 0.01, and P < 0.001, respectively, compared with the control group. #, ##, and ### indicate statistical significance at P < 0.05, P < 0.01, and P < 0.001, respectively, compared with the HCQ group. $$$ indicates statistical significance at P < 0.001 compared with the HFD group).