Beneficial Effects of a Low-dose of Conjugated Linoleic Acid on Body Weight Gain and other Cardiometabolic Risk Factors in Cafeteria Diet-fed Rats

Abstract

Conjugated linoleic acid (CLA) is a dietary supplement that has been shown to improve obesity. However, some authors have associated high doses of CLA supplementation with liver impairment and insulin resistance. The aim of this study was to assess whether the consumption of low doses of CLA maintained the beneficial effects on the main metabolic disturbances associated with metabolic syndrome (MetS) but prevented the occurrence of non-desirable outcomes associated with its consumption. Male Wistar rats, fed standard or cafeteria (CAF) diet for 12 weeks, were supplemented with three different low doses of CLA in the last three weeks. Both biochemical and H¹ NMR-based metabolomics profiles were analysed in serum and liver. The consumption of 100 mg/kg CLA, but not doses of 200 and 300 mg/kg, ameliorated the increase in body weight gain as well as the serum concentrations of glucose, insulin, cholesterol, triglyceride, diglyceride, and total phospholipid induced by a CAF diet. In turn, CLA reverted the increase in lactate, alanine, and glucose concentrations in the liver of these animals, but enhanced hepatic cholesterol accumulation without any detrimental effect on liver function. In conclusion, a low dose of CLA corrected the adverse effects associated with MetS without compromising other metabolic parameters.

Keywords: CLA; NAFLD; insulin resistance; leptin; metabolomics; obesity.

Figure 1

A scheme of the distribution of animals in the study. During the first nine weeks, one group was fed the standard chow diet (STD group), whereas the other group was fed the cafeteria diet (CAF group). After nine weeks, the animals were orally administered either vehicle (VH) or conjugated linoleic acid (CLA) at three doses (100, 200 and 300 mg/kg). On week twelve, the animals were sacrificed. CAF: cafeteria diet; CLA: conjugated linoleic acid; STD: standard chow diet; VH: vehicle.

Figure 2

Metabolic parameters. The rats were fed the STD or CAF diet for 9 weeks and then were treated orally with CLA (100, 200 or 300 mg per kg bw) for 3 weeks. (A) Body weight gain (g) from the first, second and third week of the supplementation until the last day. (B) and (C) Body composition (%) assessed by NMR, including fat and lean content, respectively. (D) Serum levels of leptin. Data are expressed as the mean ± SEM. ^a,b,c denotes p < 0.05 assessed by one-way ANOVA and Duncan’s post hoc test. CAF: cafeteria diet; NMR: nuclear magnetic resonance; CLA: conjugated linolenic acid; STD: standard chow diet; bw: body weight.

Figure 3

Glucose metabolism. The rats were fed the STD or CAF diet for 9 weeks and then were treated orally with CLA at 100 mg per kg of bw for 3 weeks. (A) Serum insulin and (B) serum glucose levels. The panels from (C–F) show liver metabolite levels of glucose, alanine, lactate and diglycerides, respectively. Data are expressed as the mean ± SEM. ^a,b denotes p < 0.05 assessed by one-way ANOVA and Duncan’s post hoc test. CAF: cafeteria diet; CLA: conjugated linolenic acid; STD: standard chow diet.

Figure 4

Serum lipid profile. The rats were fed the STD or CAF diet for 9 weeks and then were treated orally with CLA at 100 mg per kg of bw for 3 weeks. The panels from (A–F) show metabolite levels of different forms of cholesterol, triglycerides, diglycerides and total phospholipids, respectively. Data are expressed as the mean ± SEM. ^a,b,c denotes p < 0.05 assessed by one-way ANOVA and Duncan’s post hoc test. CAF: cafeteria diet; CLA: conjugated linolenic acid; STD: standard chow diet.

Figure 5

Liver function. The rats were fed the STD or CAF diet for 9 weeks and then were treated orally with CLA at 100 mg per kg of bw for 3 weeks. (A) GOT and (B) GPT serum enzymatic activities. (C) Representative histological sections of liver from from STD, CAF and CLA groups. Hepatic (D) Ccl2 and (E) Tnf-α relative gene expression. Data are expressed as the mean ± SEM. ^a,b denotes p < 0.05 assessed by one-way ANOVA and Duncan’s post hoc test. CAF: cafeteria diet; CLA: conjugated linolenic acid; STD: standard chow diet; GOT: Glutamic oxaloacetic transaminase; GPT: glutamate pyruvate transaminase.

Figure 6

Hepatic cholesterol metabolism. The rats were fed the STD or CAF diet for 9 weeks and then were treated orally with CLA at 100 mg per kg of bw for 3 weeks. The panels from (A–C) show metabolite levels of different forms of cholesterol including total, esterified and free cholesterol, respectively. The panels from (D–G) illustrate the hepatic relative gene expression levels of Asbt, Ldlr, Cyp7a1 and Hmgcr, respectively. Data are expressed as the mean ± SEM. ^a,b denotes p < 0.05 assessed by one-way ANOVA and Duncan’s post hoc test. CAF: cafeteria diet; CLA: conjugated linolenic acid; STD: standard chow diet.