A 6-month lifestyle-based weight-reduction program in adults with obesity and insulin resistance was associated with metabolic improvement, reduced oxidative stress, and partial attenuation of obesity-related low-grade inflammation, with sex-related patterns of immunometabolic adaptation to weight reduction.
Key Findings
Results
Both women and men showed significant reductions in key anthropometric and metabolic parameters following the six-month weight-reduction program.
Significant reductions were observed in body mass, BMI, waist circumference, visceral fat area (VFA), and body fat mass (BFM) in both sexes.
Both sexes showed significant decreases in fasting glucose and HOMA-IR, indicating improved insulin sensitivity.
The modified Atherogenic Index of Plasma (new-AIP) decreased significantly in both women and men.
Oxidative stress markers malondialdehyde (MDA) and Oxidative Stress Index (OSI) decreased significantly in both sexes.
The study included 36 participants (24 women and 12 men) with HOMA-IR ≥ 2 at baseline.
Results
Sex-specific metabolic differences emerged, with women showing additional body composition changes and men showing HDL-C improvement.
Women additionally showed significant decreases in fat-free mass (FFM), skeletal-muscle mass (SMM), and total body water (TBW), which were not observed in men.
Women showed significant decreases in glycated hemoglobin A1c (HbA1c) and triacylglycerols following the intervention.
Cholesterol in high-density lipoproteins (HDL-C) increased significantly only in men.
These divergent outcomes suggest sex-related patterns of metabolic adaptation to weight reduction.
Results
IL-1ra, IL-6, and TNF-α decreased significantly in both women and men following the weight-reduction program.
Reductions in IL-1ra, IL-6, and TNF-α were observed in sex-stratified analyses for both sexes.
These cytokine reductions indicate partial attenuation of obesity-related low-grade inflammation in both sexes.
The finding that these three cytokines decreased in both groups represents the shared inflammatory response to weight loss across sexes.
Results
IL-1β decreased significantly only in women, representing a sex-specific cytokine response to weight loss.
IL-1β reduction was observed in sex-stratified analyses exclusively in women.
This finding was not replicated in men despite both sexes undergoing the same weight-reduction program.
IL-1β is a pro-inflammatory cytokine, and its selective reduction in women suggests sex-related differences in immunometabolic adaptation.
Results
IL-7 decreased significantly only in men, representing another sex-specific cytokine response to the intervention.
IL-7 reduction was observed in sex-stratified analyses exclusively in men.
This sex-specific finding was observed despite both sexes following the same individualized low-calorie diet combined with moderate physical activity and health education.
The authors describe cytokine changes overall as 'selective rather than uniform.'
Methods
The weight-reduction program consisted of an individualized low-calorie diet combined with moderate physical activity and health education over six months.
Participants were required to have a HOMA-IR ≥ 2 at baseline to be eligible.
The study included 36 participants total: 24 women and 12 men.
Anthropometric, body composition, biochemical, oxidative stress, and cytokine parameters were evaluated before and after the intervention.
The trial was retrospectively registered on ClinicalTrials.gov (NCT07645105) on 11 June 2026.
Conclusions
The authors caution that findings should be interpreted carefully due to small sex-stratified subgroup sizes and the number of cytokine endpoints analyzed.
The sex-stratified subgroups were relatively small (24 women, 12 men).
The authors note that findings 'require confirmation in larger, sex-balanced studies.'
The number of cytokine endpoints analyzed is flagged as a limitation requiring cautious interpretation.
The study design did not include a control group, as all participants received the intervention.
What This Means
This research examined how a six-month weight-loss program affects inflammation and metabolism differently in women and men who have obesity and insulin resistance. Thirty-six participants (24 women and 12 men) followed an individualized low-calorie diet combined with moderate exercise and health education. The researchers measured a wide range of outcomes including body composition, blood sugar control, blood fats, markers of cellular damage from oxidative stress, and immune signaling proteins called cytokines, both before and after the program.
The study found that both women and men benefited from the program in many ways: both groups lost body fat, reduced waist size, improved blood sugar and insulin resistance, and showed lower levels of oxidative stress and several inflammatory proteins (IL-1ra, IL-6, and TNF-α). However, some differences appeared between the sexes. Women also lost lean mass (muscle and water weight), saw improvements in long-term blood sugar control (HbA1c) and triglycerides, and had reductions in an additional inflammatory protein (IL-1β). Men, on the other hand, showed increases in 'good' HDL cholesterol and reductions in a different immune protein (IL-7) that were not seen in women. This suggests that while weight loss broadly improves health in both sexes, the specific ways the body's immune and metabolic systems respond may differ between women and men.
This research suggests that sex may be an important factor to consider when designing and evaluating weight-loss interventions for people with obesity and insulin resistance. The different patterns of cytokine and metabolic changes between women and men hint that personalized approaches accounting for sex could potentially improve outcomes. However, the authors themselves emphasize that the study had relatively small numbers of participants in each sex group and that these findings need to be confirmed in larger, more balanced studies before firm conclusions can be drawn.
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Dydoń M, Birková A, Dolibog P, Čižmárová B, Hubková B, Czuba Z, et al.. (2026). Sex-Specific Cytokine Responses and Metabolic Adaptation to Weight Loss in Obesity with Insulin Resistance.. Nutrients. https://doi.org/10.3390/nu18121982