Fish oil can prevent damage to health caused by high-fat diet

Results of experiments with mice have been published by Brazilian researchers in The Journal of Physiology.

By Karina Toledo  |  Agência FAPESP – Dietary supplementation with fish oil, which is rich in polyunsaturated fatty acids of the omega-3 family, can help prevent diabetes, dyslipidemia, and other health problems caused by eating fatty foods.

This is the main finding of a study conducted with mice at the Federal University of São Paulo (UNIFESP) in Brazil. The results of the research project, which was supported by FAPESP, have been published in The Journal of Physiology.

“It’s important to note that we used a prevention model, starting supplementation when the animals were healthy. At present, we’re investigating the effect of fish oil on obese animals, and the results appear to be different,” said Maria Isabel Cardoso Alonso-Vale, a professor in UNIFESP’s Department of Biological Sciences.

The experiments were conducted during the Master’s and PhD research of Roberta Dourado Cavalcante da Cunha de Sá, supervised by Alonso-Vale.

The mice received dietary fish oil supplementation for 12 weeks. For eight weeks starting in week five, they were fed a high-fat diet consisting of 59% fat, compared with 9% for the control diet.

“The animals received 2 grams of fish oil per kilogram of body weight three times a week. Each gram of fish oil used in the study contained 540 milligrams of eicosapentaenoic acid (EPA) and 100 milligrams of docosahexaenoic acid (DHA). The proportions of these polyunsaturated fatty acids should be taken into consideration when evaluating the results,” Alonso-Vale said.

According to the scientific literature, EPA acts as an anti-inflammatory agent in the organism, inducing the production of prostaglandin E3 (PGE3), and DHA is an anti-oxidant.

Results

At the end of the 12 weeks, the weight of the mice fed the high-fat diet without supplementation with fish oil had increased twelvefold on average. Moreover, they displayed glucose intolerance, increased levels of fasting blood sugar and insulin, and increased levels of total cholesterol and LDL (low-density lipoprotein, known as “bad cholesterol”). To make matters worse, the obese rodents were eating more than the others and expending less of the energy ingested.

In the case of the group that received fish oil before and during the high-fat diet period, body weight rose eightfold on average, 30% less than the group that did not receive fish oil, and neither changes in glucose metabolism nor dyslipidemia were observed.

The next step involved in vitro measurement of metabolic parameters associated with the development of insulin resistance in adipose cells taken from subcutaneous and visceral adipose tissue. Each type of adipocyte (subcutaneous and visceral) was evaluated separately.

The results showed that a high-fat diet affects these two fat depots differently, although in both cases the researchers observed adipocyte hypertrophy and loss of function.

Subcutaneous adipocytes play a key role in capturing blood sugar, for example. This capacity was adversely affected by the high-fat diet owing to reduced expression of GLUT4, a glucose transporter protein in cell membranes.

Another alteration they observed in subcutaneous adipocytes was increased secretion of two pro-inflammatory cytokines: tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). Conversely, there was a decrease in production of adiponectin, an adipocyte-derived plasma protein with anti-inflammatory activity and an important role in the regulation of fatty acid and glucose metabolism.

In visceral adipocytes, they observed an increase in lipolysis, the breakdown of fats and other lipids by hydrolysis to release fatty acids into the bloodstream, potentially contributing to the development of dyslipidemia. Conversely, there was a decrease in the endogenous synthesis of fatty acids from carbohydrate, known as de novo lipogenesis. This mechanism, which helps avoid an excess of glucose in the organism, was impaired. They also observed increased secretion of inflammatory molecules TNF-α, IL-6 and resistin.

“A review of the literature suggests the chronic inflammation seen in the adipose tissue of obese individuals could be linked to infiltration of immune cells, especially macrophages, by white adipose tissue, which could explain much of the secretion of inflammatory cytokines. Looking at adipocytes in isolation, our study showed there was inflammation independently of the presence of these cells in tissue,” Alonso-Vale said.

Fish oil supplementation prevented metabolic alterations in both the subcutaneous and visceral adipose tissue of the mice fed a high-fat diet.

“Prescribing fish oil as a supplement, in conjunction with other strategies, could be recommended as a public health measure to prevent insulin resistance and type 2 diabetes. Of course, more research is needed before this is possible. For example, the right dose and frequency has to be established, as well as the best time to introduce supplementation,” Alonso-Vale concluded.

The article “Fish oil prevents changes induced by a high-fat diet on metabolism and adipokine secretion in mice subcutaneous and visceral adipocytes”, published in The Journal of Physiology, can be retrieved at onlinelibrary.wiley.com/doi/10.1113/JP272541/full.