Obesity affects the adaptability of adipose tissue (AT), impairing its ability to regulate energy and metabolism. Obesity is associated with many metabolic disorders, including dyslipidemia, hypertension, sleep disorders, non-alcoholic liver disease, and some types of cancer. Toll-like receptors (TLRs) are important in obesity and related metabolic disorders. TLRs are pattern-recognizing receptors (PRRs) involved in the innate immune system and recognize pathogen-associated molecular patterns (PAMPs) and endogenous ligands. TLRs, especially TLR2 and TLR4, are activated by fatty acids, endotoxins, and other ligands. TLR2 and TLR4 activation triggers inflammatory responses. Chronic inflammation driven by TLR activation is a hallmark of obesity and metabolic diseases. The inflammatory response triggered by TLR activation alters insulin signaling, contributing to insulin resistance, a key feature of metabolic syndrome and type 2 diabetes. Modulation of TLR activity through lifestyle changes (diet and exercise), obesity surgery, and pharmacological agents is under study as a possible therapeutic approach to controlling obesity and its complications.

Metabolically healthy (MH) and metabolically unhealthy (MUH) phenotypes can be present in any subject independently of their body mass index (BMI). However, factors related to the presence of these phenotypes are poorly understood. Therefore, the aim of this cross-sectional study is to describe the prevalence and characteristics associated with the MH and MUH phenotypes in Mexican subjects with different BMI categories. Anthropometric and biochemical parameters were evaluated after 12 h of fasting. HMW (High Molecular Weight) adiponectin and insulin levels were measured by ELISA (enzyme-linked immunosorbent assay). A total of 345 subjects were included, of which, 73.9% were women. The prevalence of the MH phenotype was 69.9%, 46.7%, and 19% in normal weight, overweight, and obesity, respectively. ROC (receiver operating characteristic) curve analysis showed that the waist circumference demonstrated a statistical significance (p < 0.01) in detecting the MUH phenotype in each BMI group only in women. Furthermore, subjects with lower HMW adiponectin levels showed a 2.1 increased risk of presenting the MUH phenotype. In conclusion, in this Mexican population, waist circumference was an anthropometric parameter that identified women with the MUH phenotype in all BMI categories and hypoadiponectinemia was a risk factor for the presence of this phenotype.

Background: An unbalanced dietary intake of omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) has been associated with chronic inflammation and oxidative stress, both of which contribute to the pathophysiology of obesity. Objective: We aimed to evaluate the effects of a diet with an n-6:n-3 PUFA ratio of 5:1 on body composition, biochemical parameters, and the gene expression of cytokines and antioxidant enzymes in a murine model of diet-induced obesity. Methods: A diet-induced obesity model was established in C57BL6/J mice over 17 weeks. Mice were then fed different diets for 8 weeks: a control diet (chow), a high-fat diet with a 30:1 n-6:n-3 ratio (HFD-30:1), and a high-fat diet enriched with n-3 fatty acids, with a 5:1 n-6:n-3 ratio (HFD-5:1). Body weight and food intake were monitored throughout this study. Biochemical parameters were measured, and the expression of antioxidant enzymes and cytokine genes was analyzed by qPCR. Data were analyzed using GraphPad Prism software. Results: The HFD-5:1 group exhibited a significant reduction in body weight (p = 0.0182), liver tissue weight (p = 0.01), serum glucose levels (p = 0.010), area under the curve (AUC) (p = 0.0161), cholesterol (p < 0.0001), and triglycerides (p = 0.0069) compared to the HFD-30:1 group. The body weight in the HFD-5:1 group decreased to levels comparable to the control group. Additionally, the expression of the inflammatory cytokine genes Ccl2 (p = 0.0389) and Tgfb1 (p = 0.0226) was significantly reduced. Conclusions: These findings suggest that adjusting the dietary n-6:n-3 ratio to 5:1 modulates inflammation-related gene expression and improves metabolic markers in obese mice, supporting its potential relevance for future translational research.

Background/Objectives: Obesity is associated with chronic low-grade inflammation. Polyunsaturated fatty acids (PUFAs) such as omega-3 (n-3), are essential in anti-inflammatory processes. Therefore, the aim of this study was to evaluate the effect of a dietary intervention along with supplementation of 1.8 g of marine n-3 PUFAs on anthropometric, biochemical, and inflammatory markers in adults. Methods: An 8-week double-blind randomized clinical trial was conducted with a diet (200 kcal/day reduction each 4 weeks based on the estimated basal caloric expenditure) containing a n-6/n-3 PUFA ratio ≤ 5:1, along with daily 1.8 g of marine n-3 supplementation (EPA and DHA) vs. active placebo 1.6 g (ALA). A total of 40 subjects were included in the study, 21 in the marine omega-3 group and 19 in the active placebo group. Inclusion criteria included subjects aged 25 to 50 years with obesity as determined by body mass index (BMI) and/or abdominal obesity according to ATP III criteria. Results: The marine omega-3 supplemented group had a better effect compared to the active placebo group, increasing Resolvin D1 [129.3 (−90.1–193.5) vs. −16.8 (−237.8–92.5) pg/mL, p = 0.041], IL-10 [1.4 (−0.7–4.6) vs. −2.0 (−5–0.05) pg/mL, p = 0.001], and decreasing IL-6 [−0.67 (2.72–−0.59) vs. 0.03 (−0.59–1.84) pg/mL, p = 0.015], and MCP-1 [−29.6 (−94.9–5.50) vs. 18.3 (−97.3–66.35) pg/mL, p = 0.040]. Conclusions: A diet supplemented with marine n-3 improves inflammatory markers by increasing systemic levels of Resolvin D1 and IL-10 and decreasing IL-6 and MCP-1.