Supplementation with bioactive compounds capable of regulating energy homeostasis is a promising strategy to manage obesity. Here, we have screened the ability of different phenolic compounds (myricetin, kaempferol, naringin, hesperidin, apigenin, luteolin, resveratrol, curcumin, and epicatechin) and phenolic acids (p-coumaric, ellagic, ferulic, gallic, and vanillic acids) regulating C. elegans fat accumulation. Resveratrol exhibited the strongest lipid-reducing activity, which was accompanied by the improvement of lifespan, oxidative stress, and aging, without affecting worm development. Whole-genome expression microarrays demonstrated that resveratrol affected fat mobilization, fatty acid metabolism, and unfolded protein response of the endoplasmic reticulum (UPR^ER), mimicking the response to calorie restriction. Apigenin induced the oxidative stress response and lipid mobilization, while vanillic acid affected the unfolded-protein response in ER. In summary, our data demonstrates that phenolic compounds exert a lipid-reducing activity in C. elegans through different biological processes and signaling pathways, including those related with lipid mobilization and fatty acid metabolism, oxidative stress, aging, and UPR-ER response. These findings open the door to the possibility of combining them in order to achieve complementary activity against obesity-related disorders.

Background/Objectives: Collagen is a protein formed by very long amino acid chains. When conveniently treated, it can incorporate water into the net, thus increasing its volume and mass. The present work aimed to evaluate the potential anti-obesity effects of bovine collagen that has been technologically treated to increase its water retention capacity in an acid pH medium, with the objective of inducing satiation. Methods: Collagen’s digestibility was tested with a pepsin digestion test. Its swelling capacity was tested in an acid pH medium simulating gastric conditions. Postprandial levels of ghrelin in response to collagen supplementation were tested in rats. In a randomized control trial, 64 subjects with overweight/obesity were allocated in two groups: supplemented daily with two protein bars enriched with collagen (20 g per day) for 12 weeks, or control group. Anthropometric and biochemical measurements were assessed in all the participants. Results: This collagen showed a low digestibility (1900%) in vitro. In humans with overweight and obesity, this collagen significantly reduced body weight, body mass index (BMI), systolic blood pressure (SBP), and fatty liver index (FLI) and increased fat-free mass when compared with the control group. A significant reduction in the sarcopenic index; total, troncular, and visceral fat (measured by DEXA); and serum leptin levels were observed in the collagen group at the end of the intervention, with no differences with respect to controls. Collagen reduced the sensation of hunger and increased fullness and satisfaction. In male Wistar rats, collagen decreased postprandial blood ghrelin levels. Conclusions: Collagen supplementation (20 g per day for 12 weeks) reduced body weight, BMI, waist circumference, fat mass, FLI, and SBP in humans with overweight and obesity, which might be related to the increased sensation of fullness and satisfaction reported by the volunteers after the intake.

This study aims to analyze the relationship between gut microbiota composition and health parameters through specific biochemical markers and food consumption patterns in the Spanish population. This research includes 60 Spanish adults aged 47.3 ± 11.2 years old. Biochemical and anthropometric measurements, and a self-referred dietary survey (food frequency questionnaire), were analyzed and compared with the participant´s gut microbiota composition analyzed by 16s rDNA sequencing. Several bacterial strains differed significantly with the biochemical markers analyzed, suggesting an involvement in the participant´s metabolic health. Lower levels of Lactobacillaceae and Oscillospiraceae and an increase in Pasteurellaceae, Phascolarctobacterium, and Haemophilus were observed in individuals with higher AST levels. Higher levels of the Christensenellaceae and a decrease in Peptococcaceae were associated with higher levels of HDL-c. High levels of Phascolarctobacterium and Peptococcus and low levels of Butyricicoccus were found in individuals with higher insulin levels. This study also identified associations between bacteria and specific food groups, such as an increase in lactic acid bacteria with the consumption of fermented dairy products or an increase in Verrucomicrobiaceae with the consumption of olive oil. In conclusion, this study reinforces the idea that specific food groups can favorably modulate gut microbiota composition and have an impact on host´s health.

Probiotic strains with health-promoting activities have emerged as a promising strategy to prevent or treat different metabolic syndrome-related disturbances, including obesity or type 2 diabetes. In this work, we characterize the probiotic properties of a novel strain of Latilactobacillus sakei (L. sakei) CNTA 173, and we demonstrate its anti-obesity properties using the in vivo model Caenorhabditis elegans (C. elegans). This new strain exhibited sensitivity to the entire spectrum of antibiotics analysed, gastric and intestinal in vitro resistance, β-galactosidase activity, and the ability to form biofilm and to produce acetic acid in vitro. Cell culture analyses demonstrated that L. sakei CNTA 173 was able to reduce the adhesion to Caco-2 cells of the pathogenic E. coli O157:H7 and to exert immunomodulatory capacity in RAW 264.7 and HT-29 in vitro models. Furthermore, supplementation with L. sakei CNTA 173 counteracted the deleterious effects of glucose in C. elegans by significantly reducing fat accumulation, enhancing the oxidative stress response, and extending lifespan by directly regulating the carbohydrate and lipid metabolism-related genes acox-1, maoc-1, and daf-16. Our results unveil new strain-specific mechanisms of action by which L. sakei CNTA 173 exerts beneficial effects in vitro and in C. elegans, and suggest potential application of this novel probiotic strain in the prevention and treatment of metabolic syndrome-related disturbances.

Collagen supplementation (CS) has emerged as a promising therapeutic approach with potential benefits for managing metabolic syndrome (MetS)-related risk factors. This narrative review integrates human evidence with preclinical mechanistic insights into the metabolic actions of collagen. Anti-obesity effects are attributed to increased satiety, gastric distension, GLP-1 secretion and enhanced fatty acid oxidation mediated by PPAR-α activation and AMPK signalling. In type 2 diabetes, collagen improves glucose homeostasis by enhancing insulin sensitivity, upregulating GLUT-4 and inhibiting dipeptidyl peptidase IV (DPP-IV), thereby prolonging incretin activity (GLP-1 and GIP) and supporting β-cell function. The antihypertensive effect of collagen peptides (CP) is primarily linked to angiotensin-converting enzyme (ACE) inhibition, which reduces angiotensin II levels while promoting bradykinin-mediated vasodilation and nitric oxide release. In addition, CP has shown potential in improving lipid profiles by modulating PPAR-γ and AMPK, increasing HDL-C and reducing LDL-C and triacylglycerols. Emerging evidence also supports a role for collagen in restoring gut microbiota balance, increasing short-chain fatty acid production and reducing pro-inflammatory and oxidative pathways, contributing to systemic metabolic regulation. Overall, these findings suggest CS exerts multi-targeted benefits on MetS components through modulation of endocrine, inflammatory and metabolic pathways. Nevertheless, larger, long-term clinical trials are warranted to determine optimal dosing regimens, evaluate long-term efficacy, and further elucidate microbiota-mediated effects.

Collagen and its derivatives, including hydrolyzed collagen peptides, have emerged as promising bioactive compounds with potential benefits in obesity and metabolic syndrome prevention and management. This study aimed to evaluate the potential effects of a low-molecular-weight bovine collagen hydrolysate (COLLinstant^® LMW) on metabolic health using Caenorhabditis elegans and C57BL/6 diet-induced obese mice. In C. elegans, C-LMW (2 mg/mL) improved healthspan by significantly reducing fat accumulation (as measured with Nile Red) and reactive oxygen species measured through dihydroethidium, slowing the aging process measured with lipofuscin, and extending the median lifespan of the nematodes. In 32 male 20-week-old diet-induced obese mice, C-LMW supplementation (1 mg/animal/day) for 8 weeks led to a significant reduction in mesenteric, visceral and total adipose tissue (−28% −15% and −18%, respectively; p > 0.05), improved glucose tolerance, and partially restored glucose homeostasis, as demonstrated by intraperitoneal glucose tolerance (−26% AUC, p < 0.05). Additionally, collagen hydrolysate supplementation led to a significant impact on gut microbiota composition by increasing microbial diversity and modulating beneficial bacterial populations, which may contribute to the observed metabolic improvements. These findings suggest that bovine-derived collagen peptides exert anti-obesogenic and metabolic regulatory effects, supporting their potential as functional dietary ingredients for obesity management.