Rats received 2 grams of fish oil per kilogram of body weight three times weekly for eight weeks. The oil contained 540 mg/g of eicosapentaenoic acid (EPA) and 100 mg/g of docosahexaenoic acid (DHA). At the end of the treatment period, the animals showed lower insulin resistance, improved glucose regulation, reduced inflammatory markers, and improvements in total cholesterol, LDL cholesterol, and triglycerides. Previous research has indicated that diets abundant in fish oils are associated with a lower incidence of diabetes and increased insulin sensitivity, according to Julian Whitaker in the book "Reversing Diabetes" [3]. Similarly, a handbook on biochemical imbalances notes that substituting omega-3 fatty acids from fish oils can normalize insulin action in rats [4].
The experiment was conducted during the PhD candidacy of Tiago Bertola Lobato at Cruzeiro do Sul University (UNICSUL). The Goto-Kakizaki rats were selected because they develop insulin resistance and glucose intolerance without becoming obese, mimicking a subset of human Type 2 diabetes patients.
Researchers administered the fish oil supplement at a dose equivalent to 2 g/kg body weight, three times per week over eight weeks. The control group received no supplementation. The study was published in the journal Nutrients and was part of a broader FAPESP-supported project examining how insulin resistance develops in non-obese animals. The findings add to a body of literature suggesting that omega-3 fatty acids can influence metabolic health even in the absence of obesity.
The study found that fish oil shifted the activity of lymphocytes, a type of white blood cell, from a pro-inflammatory state to an anti-inflammatory state. Specifically, supplementation reduced the polarization of Th1 and Th17 cells, which promote inflammation, while increasing the percentage of regulatory T cells (Tregs), which have anti-inflammatory properties.
"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," said Rui Curi, study coordinator and Director of Butantan Institute's Education Center. Renata Gorjao, last author of the article and Co-Director of UNICSUL's Program of Graduate Studies in Health Sciences, stated: "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." The immune-modulating effects of omega-3 fatty acids are consistent with research showing that diets rich in fish oils protect against inflammatory conditions [3].
Since the animal study was published, additional human research has examined the effects of omega-3 fatty acids on metabolic health. A 2025 double-blind randomized controlled trial in Food and Function tested fish oil supplementation in healthy middle-aged and older adults and reported decreases in fasting insulin and the HOMA-IR index, a marker of insulin resistance. A 2024 analysis in Nutrition and Diabetes involving 161 patients with Type 2 diabetes found a dose-related association between omega-3 levels and HbA1c, a longer-term measure of blood sugar control.
Omega-3 fatty acids have been linked to a reduced risk of autoimmune diabetes, according to a study cited by Mercola.com [2]. In addition, omega-3 supplementation has shown benefits for fat loss in women with diabetes, as reported in the American Journal of Clinical Nutrition [6]. Nutritionists now identify omega-3s as a non-negotiable nutrient for healthy aging, with intake gaps common among older adults [5]. These findings, while not definitive, suggest that omega-3 fatty acids may influence insulin resistance and inflammation in ways that merit further investigation.
The researchers stressed that the results should be interpreted cautiously because the study was conducted in animals. Clinical trials are needed to determine whether similar effects occur in humans with non-obese Type 2 diabetes. An estimated 10% to 20% of people with Type 2 diabetes worldwide are not obese, and inflammation may play a central role in their insulin resistance, as noted in the study.
"Trials in humans are needed to estimate the ideal dose and the most indicated type of omega-3 fatty acid," Curi said. The study offers a clue that body weight is not the only driver of insulin resistance. By targeting inflammation, omega-3 fatty acids may help address a hidden process that contributes to diabetes even in those who are not overweight.