Fish oil may have a surprising role in the fight against insulin resistance, especially in a form of type 2 diabetes that is often overlooked. A Brazilian study published in Nutrients found that omega-3 fatty acids from fish oil reduced glucose intolerance and weakened insulin resistance in rats that were not obese but showed a diabetes-like metabolic condition.
The work was funded by FAPESP and focused on Goto-Kakizaki rats, a well established animal model used to study non-obese type 2 diabetes. Type 2 diabetes is marked by high blood sugar that occurs when insulin, the hormone that helps move glucose from the blood into cells, does not work effectively.
Fish Oil and Insulin Resistance
Omega-3 supplements, including fish oil, are often used by people with cardiovascular disease and type 2 diabetes. However, scientists still know much less about how these fatty acids affect insulin resistance when obesity is not involved.
That question matters because obesity is one of the strongest risk factors for type 2 diabetes, but it is not the whole story. An estimated 10% to 20% of people with type 2 diabetes worldwide are not obese. For these patients, the biological roots of insulin resistance may differ from the better known obesity-linked pathways.
In the study, researchers gave the rats fish oil at a dose of 2 grams per kilogram of body weight (equivalent to 540 mg/g of eicosapentaenoic acid, or EPA, and 100 mg/g of docosahexaenoic acid, or DHA) three times weekly for eight weeks. By the end of the experiment, the treated animals showed lower insulin resistance, better blood sugar control, reduced inflammatory markers, and improvements in several lipid measures, including total cholesterol, LDL (“bad cholesterol”) and triglycerides.
The results came from preclinical experiments, so they do not prove that fish oil will have the same effects in people. Still, the findings point to inflammation as a powerful target in non-obese diabetes and suggest that omega-3 fatty acids deserve closer study in this group.
A Shift in Immune Cells
“Our experiments involved Goto-Kakizaki [GK] rats, an animal model for non-obese type 2 diabetes. 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,” said Rui Curi, Director of Butantan Institute’s Education Center, Professor of Interdisciplinary Graduate Studies in Health Sciences at Cruzeiro do Sul University (UNICSUL), and coordinator of the study.
Lymphocytes are white blood cells that help direct the adaptive immune response. When their behavior changes, the effects can spread through the immune system and influence other cells involved in inflammation.
“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. In such cases, these cells produce more pro-inflammatory cytokines, as is central in obese people with diabetes,” Curi explained.
“The main aim of the study, therefore, was to find out whether supplementation with fish oil [rich in omega-3] could reverse specific alterations in lymphocytes that had been observed in previous research. 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,” said Renata Gorjão, last author of the article, and Co-Director of UNICSUL’s Program of Graduate Studies in Health Sciences.
Inflammation Without Obesity
The Nutrients study, conducted during the PhD candidacy of Tiago Bertola Lobato, was part of a broader FAPESP-supported project exploring how insulin resistance develops in non-obese animals.
Curi noted that obesity is a major diabetes risk factor, but not the only one. In people who develop diabetes without obesity, one leading hypothesis is that genetic factors may play an important role. In another study published in Cells, Curi, Gorjão, and colleagues investigated whether delayed intestinal transit might also contribute to insulin resistance in non-obese individuals.
“Most obese people have chronic low-level inflammation, which is known to affect the insulin signaling pathways. 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,” Curi said.
The group had previously shown systemic inflammation in non-obese GK rats with insulin resistance in a study published in the International Journal of Molecular Sciences.
