Fish oil may play an amazing role in the fight against insulin resistance, especially the often-overlooked type 2 diabetes. Brazilian study published in nutrients They found that omega-3 fatty acids derived from fish oil reduced glucose intolerance and weakened insulin resistance in non-obese rats with a metabolic condition similar to diabetes.
The study was funded by FAPESP and focused on the Goto-Kakizaki rat, an established animal model used to study non-obese type 2 diabetes. Type 2 diabetes is characterized by high blood sugar, which occurs when insulin, the hormone that helps move glucose from the blood to cells, does not work effectively.
Fish oil and insulin resistance
Omega-3 supplements, including fish oil, are often used by people with cardiovascular disease or type 2 diabetes. However, scientists still know little about how these fatty acids affect insulin resistance when obesity is not involved.
This question is important because obesity is one of the strongest risk factors for type 2 diabetes, but it’s not the only one. An estimated 10% to 20% of people with type 2 diabetes worldwide are not obese. For these patients, the biological causes of insulin resistance may be different from the well-known obesity-related pathways.
In this study, researchers gave rats 2 grams of fish oil per kilogram of body weight (equivalent to 540 mg/g of eicosapentaenoic acid (EPA) and 100 mg/g of docosahexaenoic acid (DHA)) three times a week for eight weeks. By the end of the experiment, treated animals showed reduced insulin resistance, improved blood sugar control, decreased inflammatory markers, and improvements in several lipid measurements, including total cholesterol, LDL (“bad cholesterol”), and triglycerides.
These results are from preclinical experiments and do not prove that fish oil has the same effect on humans. Still, the findings point to inflammation as a strong target in non-obese diabetes and suggest that omega-3 fatty acids deserve to be studied more closely in this group.
Changes in immune cells
“Our experiments included Goto-Kakizaki (GK) rats, a non-obese animal model of type 2 diabetes. We found that we can reduce insulin resistance in these animals by modulating the inflammatory response to change the profile of defense cells (lymphocytes) from a pro-inflammatory state to an anti-inflammatory state. This process is similar to the response to omega-3 fatty acid supplementation in insulin-resistant obese individuals,” said Louis Kuri. Director of the Education Center of the Butantan Research Institute, professor and research coordinator at the Interdisciplinary Graduate School of Health Sciences at the University of Cruzeiro do Sul (UNICSUL).
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 affect other cells involved in inflammation.
“Previous studies have observed changes in both lymphocytes and macrophages (large white blood cells that are abundant in adipose tissue and are part of the innate immune system that engulf and destroy pathogens) in non-obese rats with insulin resistance. In these cases, these cells produce more pro-inflammatory cytokines, as are central to obese people with diabetes,” Professor Curi explained.
“Therefore, the main objective of this study was to investigate whether supplementation with fish oil (rich in omega-3) could reverse certain changes in lymphocytes observed in previous studies. We now know more about the sex link and confirm that this is an important factor in diabetes even in the absence of obesity,” said Renata Gorjian, last author of the paper and co-director of the UNICSUL Graduate Research Program. Health science.
Inflammation without obesity
of nutrients The study, carried out during Tiago Beltola Lobato’s PhD candidacy, was part of a broader FAPESP-supported project investigating how insulin resistance develops in non-obese animals.
Professor Kuri pointed out that while obesity is a major risk factor for diabetes, it is not the only one. A leading hypothesis is that genetic factors may play an important role in people who develop diabetes in the absence of obesity. In another study published in cellCuri, Gorjão and colleagues investigated whether delayed intestinal transit could 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 pathway. The increased adipose tissue due to obesity releases pro-inflammatory cytokines that affect the insulin signaling pathway, promoting insulin resistance. In non-obese models, this influential feature of adipose tissue is not present, but systemic inflammation is present,” Curi said.
The group previously published a study showing systemic inflammation in non-obese GK rats with insulin resistance. International Journal of Molecular Science.
Another paper from the same project reports that anti-inflammatory defenses appear to malfunction early in non-obese GK rats with insulin resistance. The lymph nodes of newly weaned 21-day-old GK puppies, part of the immune system, already showed a decrease in markers for regulatory T cells (Tregs, cells with anti-inflammatory properties). The researchers also detected other early inflammatory changes. The work was published by FEBS letterJournal of the European Federation of Biochemical Societies.
How do omega-3s help?
Nutrient research suggests that fish oil may work by shifting immune activity away from harmful inflammatory patterns and toward more protective patterns.
“Fish oil supplementation reversed this pro-inflammatory profile and exhibited a significant anti-inflammatory effect, reducing the polarization of Th1 and Th17 cells (lymphocyte subtypes that play important functions in inflammation), and subsequently resulting in an increase in the proportion of Tregs that may inhibit pro-inflammatory lymphocyte activation. In this way, omega-3 on lymphocytes The action of fatty acids modulates the lymphocytes from a pro-inflammatory state to a normal state.”It is possible that the anti-inflammatory state caused decreased insulin resistance in these animals,” Lobato said.
This change in immunity is important because insulin resistance is not just a problem of glucose metabolism. It is also closely related to inflammation. If inflammatory signals remain elevated, insulin signaling can be disrupted, making cells less responsive to the hormone.
This study further strengthens the view that type 2 diabetes is a disease shaped by both the metabolism and the immune system. In this case, fish oil appears to improve blood sugar regulation not just by changing fat levels, but by altering the inflammatory environment that promotes insulin resistance.
What was added in later research
Since then, nutrients Since the paper was published, related human studies continue to investigate how omega-3 fatty acids influence early diabetes risk and metabolic health.
Double-blind randomized controlled trial in 2025 food and function We tested fish oil supplementation in healthy middle-aged and older adults. Over 12 weeks, there was a dose-related increase in serum EPA and DHA in the fish oil group. The researchers also reported a decrease in fasting insulin and the HOMA-IR index, a common marker of insulin resistance. Fasting blood sugar levels trended lower across groups, and several lipid-related measures also improved.
Another analysis for 2024 nutrition and diabetes investigated the relationship between omega-3 levels and HbA1c, a long-term marker of glycemic control, using modeling data from 161 patients with type 2 diabetes. The authors reported a dose-related relationship and suggested that omega-3 intake could be studied in a more individualized manner, but also noted that the role of omega-3s in type 2 diabetes remains controversial.
Taken together, these studies do not resolve the question of whether fish oil should be used to manage diabetes. Human evidence remains mixed, and the Brazilian study was conducted on animals rather than humans. However, the new findings are consistent with the idea that omega-3 fatty acids may influence insulin resistance and inflammation, and merit closer examination.
Further research still needed
Despite the promising findings, the researchers stressed that the results should be interpreted with caution. While animal studies can help uncover biological mechanisms, clinical trials are needed for scientists to know whether the same strategies will work in non-obese patients with type 2 diabetes.
“These studies involved well-established experimental models that mimic insulin resistance in non-obese individuals. Human trials are needed to estimate the ideal dose and type of omega-3 fatty acids that are most applicable,” Curi said.
So far, this study provides a compelling clue: Weight may not be the only factor in insulin resistance in diabetes. Inflammation may play a central role even in the absence of obesity, and fish oil may help reveal how that hidden process changes.
