Fish oil curbs insulin resistance and glucose intolerance by modulating inflammation, study finds

New research suggests fish oil can weaken insulin resistance and reduce glucose intolerance by modulating the body’s inflammatory response. 

The study, published in the journal Nutrients, involved experiments with rats, which were not obese but exhibited a condition similar to type 2 diabetes. The disease is characterized by elevated blood sugar due to reduced action of the hormone insulin.

The authors explain supplementation with omega-3 fatty acids — such as those present in fish oil — is commonly prescribed for individuals with cardiovascular problems and type 2 diabetes.

However, the effects of these nutrients on insulin resistance without obesity are poorly understood.

“Our experiments involved Goto-Kakizaki [GK] rats, an animal model for non-obese type 2 diabetes,” explains study coordinator Rui Curi, director of Butantan Institute’s Education Center, professor of Interdisciplinary Graduate Studies in Health Sciences at Cruzeiro do Sul University (UNICSUL).

“We found that insulin resistance can be reduced in these animals by modulating the inflammatory response so as to change the profile of defense cells [lymphocytes] from a pro-inflammatory state to an anti-inflammatory state.”

“This process parallels the response of obese individuals with insulin resistance to omega-3 fatty acid supplementation,” he notes.

The study found 2 g of fish oil per kg of body weight three times per week for eight weeks reduced insulin resistance in non-obese rats.The study also highlights that these alterations in lymphocytes — white blood cells that orchestrate the adaptive immune response — tend to impact other immune system cells, triggering a cascade effect.

Hope for non-obese type 2 diabetes patients

In this study, the researchers observed that administration of 2 g of fish oil per kg of body weight three times per week for eight weeks reduced insulin resistance in non-obese rats. The rats also displayed improved levels of blood sugar, inflammatory markers, and lipid features, including total cholesterol, LDL (“bad cholesterol”), and triglycerides.

This dosage is equivalent to 540 mg/g of eicosapentaenoic acid, or EPA, and 100 mg/g of docosahexaenoic acid, or DHA.

Although the findings resulted from preclinical trials, they offer hope for non-obese type 2 diabetes patients, or 10–20% of the worldwide total with the disease, highlight the study authors.

“In previous studies, we observed alterations in both lymphocytes and macrophages [large white blood cells that often reside in adipose tissue and are part of the innate immune system, engulfing and destroying pathogens] in non-obese rats with insulin resistance,” Curi explains.

In such cases, these cells produce more pro-inflammatory cytokines, as is central in obese people with diabetes.

“The main aim of the study, therefore, was to find out whether supplementation with fish oil could reverse specific alterations in lymphocytes that had been observed in previous research,” says Renata Gorjão, last author of the article and the co-director of UNICSUL’s Program of Graduate Studies in Health Sciences.

“Our findings increased our knowledge of the link between inflammation and insulin resistance in non-obese animals, confirming that this is a key factor in diabetes even in the absence of obesity.”

Insulin resistance linked to delayed intestinal transit

According to Curi, obesity is a significant risk factor for diabetes, but not the only one. In non-obese diabetes patients, the primary hypothesis is that the cause is genetic.

In an article published in the journal Cells, Curi, Gorjão, et al. investigate the possibility that insulin resistance in the non-obese can be linked to delayed intestinal transit.

“Most obese people have chronic low-level inflammation, which is known to affect the insulin signaling pathways,” explains Curi.

“Adipose tissue, which is augmented in obesity, releases pro-inflammatory cytokines that affect the insulin signaling pathways, promoting insulin resistance. In the non-obese model, this impactful characteristic of adipose tissue is absent, but systemic inflammation is present.”

Systemic inflammation in non-obese GK rats with insulin resistance was demonstrated in a previous study published in the International Journal of Molecular Sciences.

In another article relating to the same project, the researchers reported an early breakdown of anti-inflammatory mechanisms in non-obese GK rats with insulin resistance.

Lymph nodes (part of the immune system) in newly weaned 21-day-old GK pups already exhibited a reduction in markers of regulatory T-cells (Tregs, cells with anti-inflammatory characteristics). Other early inflammatory alterations were also observed in the rats. The article is published in FEBS Letters, a journal of the Federation of European Biochemical Societies.

“Fish oil supplementation reversed this pro-inflammatory profile, displaying a significant anti-inflammatory effect and reducing polarization of Th1 and Th17 cells [lymphocyte subtypes that perform crucial functions in inflammation], followed by a rise in the percentage of Tregs, which can inhibit the activation of pro-inflammatory lymphocytes,” says Lobato.

“Thus the action of omega-3 fatty acids on lymphocytes, modulating them from a pro-inflammatory state to an anti-inflammatory state, may have triggered the reduction in insulin resistance in these animals.”

Despite the positive findings, the researchers stress that more research is needed to confirm their findings. “These studies involved well-established experimental models that mimic insulin resistance in non-obese individuals. Trials in humans are needed to estimate the ideal dose and the most indicated type of omega-3 fatty acid,” Curi concludes.

In other recent omega-3 research, a statistical analysis of 777 Swiss participants in a clinical trial found that taking one gram of omega-3 daily over three years slows biological aging by an average of 2.9–3.8 months.