The importance of metabolic health is a major societal concern due to the increasing prevalence of metabolic diseases such as obesity, diabetes, and various cardiovascular diseases. The circadian clock is clearly implicated in the development of these metabolic diseases. Indeed, it regulates physiological processes by hormone modulation, thus helping the body to perform them at the ideal time of day. Since the industrial revolution, the actions and rhythms of everyday life have been modified and are characterized by changes in sleep pattern, work schedules, and eating habits. These modifications have in turn lead to night shift, social jetlag, late-night eating, and meal skipping, a group of customs that causes circadian rhythm disruption and leads to an increase in metabolic risks. Intermittent fasting, especially the time-restricted eating, proposes a solution: restraining the feeding window from 6 to 10 h per day to match it with the circadian clock. This approach seems to improve metabolic health markers and could be a therapeutic solution to fight against metabolic diseases. This review summarizes the importance of matching life habits with circadian rhythms for metabolic health and assesses the advantages and limits of the application of time-restricted fasting with the objective of treating and preventing metabolic diseases.

Metabolic syndrome (MetS) is a major societal concern due to its increasing prevalence and its high risk of cardiovascular complications. The ketogenic diet (KD), a high fat, low carbohydrate, and non-caloric restrictive diet, is a new popular weight loss intervention but its beneficial effects are controversial. This study aims to gather all of the relevant studies using KD for metabolic disease treatment to determine its beneficial effects and evaluate its safety and efficacy for patients. Following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we included 20 articles in the final review. Overall, most of the studies showed a significant effect of KD on weight loss (17/19 articles), BMI (7/7), glucose levels (9/13), insulin levels (7/9), HOMA-IR (4/5), HbA1c (7/7), total cholesterol (6/9), TG (13/15), AST (3/4), and ALT (3/5), and no major side effects. The results heterogeneity seems to be explained by a difference of diet composition and duration. In conclusion, KD is a safety diet which seems to be a promising approach for obesity and MetS treatment, even if the optimal carbohydrate proportion and diet duration must be explored to enhance the beneficial effects of KD.

Background: Medium Chain Fatty Acids (MCFAs) are a dietary supplement that exhibit interesting properties, due to their smaller molecular size. The acute consumption of MCFAs is expected to enhance exercise performance. However, the short-term effects of MCFAs on endurance performance remains poorly understood. The aim of our study is to evaluate the octanoic acid (C8)-rich diet effect on endurance capacity, and to explore their molecular and cellular effects. Methods: C57BL/6J mice were fed with a chow diet (Control group) or an octanoic acid-rich diet (C8 diet) for 6 weeks. Spontaneous activity, submaximal and maximal exercise tests were carried out to characterize the exercise capacities of the mice. Beta-oxidation and mitochondrial biogenesis pathways were explored in skeletal muscle by RT-qPCR, Western Blot (Quadriceps) and histochemical staining (Gastrocnemius). Results: Mice fed with a C8-rich diet presented a higher spontaneous activity (p < 0.05) and endurance capacities (p < 0.05) than the control, but no effect on maximal effort was observed. They also presented changes in the skeletal muscle metabolic phenotype, with a higher number of the oxidative fibers, rich in mitochondria. At the molecular level, the C8-diet induced an AMPK activation (p < 0.05), associated with a significant increase in PGC1a and CS gene expression and protein levels. Conclusion: Our study provided evidence that C8-enrichment as a food supplementation improves endurance capacities and activates mitochondrial biogenesis pathways leading to higher skeletal muscle oxidative capacities.

Chemotherapy is a common therapy to treat patients with breast cancer but also leads to skeletal muscle deconditioning. Skeletal muscle deconditioning is multifactorial and intermuscular adipose tissue (IMAT) accumulation is closely linked to muscle dysfunction. To date, there is no clinical study available investigating IMAT development through a longitudinal protocol and the underlying mechanisms remain unknown. Our study was dedicated to investigating IMAT content in patients with early breast cancer who were treated with chemotherapy and exploring the subsequent cellular mechanisms involved in its development. We included 13 women undergoing chemotherapy. Muscle biopsies and ultrasonography assessment were performed before and after chemotherapy completion. Histological and Western blotting analyses were conducted. We found a substantial increase in protein levels of three mature adipocyte markers (perilipin, +901%; adiponectin, +135%; FABP4, +321%; P < 0.05). These results were supported by an increase in oil red O-positive staining (+358%; P < 0.05). A substantial increase in PDGFRα protein levels was observed (+476%; P < 0.05) highlighting an increase in fibro-adipogenic progenitors (FAPs) content. The cross-sectional area of the vastus lateralis muscle fibers substantially decreased (−21%; P < 0.01), and muscle architecture was altered, as shown by a decrease in fascicle length (−15%; P < 0.05) and a decreasing trend in muscle thickness (−8%; P = 0.08). We demonstrated both IMAT development and muscle atrophy in patients with breast cancer who were treated with chemotherapy. FAPs, critical stem cells inducing both IMAT development and skeletal muscle atrophy, also increased, suggesting that FAPs likely play a critical role in the skeletal muscle deconditioning observed in patients with breast cancer who were treated with chemotherapy.

Weight cycling is a major challenge in obesity management. Caloric restriction is known to promote this phenomenon, but the impact of macronutrient changes during dieting remains unclear. This study aimed to determine the role of macronutrient changes in weight maintenance without caloric restriction by alternating between two hypercaloric diets: a high-carbohydrate, high-fat Western diet (WD) and a low-carbohydrate, high-fat diet (LCHDF). Obesity was induced in 8-week-old C57BL/6 male mice by 10 weeks of WD feeding. Then, the mice were subjected to 12 weeks of LCHFD interspersed with WD (I-WD), 3 periods of 2-week LCHFD followed by 2 periods of 3-week WD, or 12 weeks of continuous WD (C-WD). C-WD and I-WD mice were compared to standard diet (SD) mice. In the I-WD group, each LCHFD period decreased weight gain, but mice regained weight after WD resumption. I-WD mice exhibited obesity, dyslipidemia, and glucose intolerance, similarly to the C-WD mice. I-WD mice also developed nonalcoholic steatohepatitis, associated with an increase in type-III collagen gene expression and a decrease in FGF21 protein levels, in comparison with SD. I-WD mice developed weight cycling despite maintaining a high caloric consumption, suggesting that changes in macronutrients during dieting are also a trigger of weight regain.

Treatment options for advanced liver disease and hepatocellular carcinoma (HCC) are limited, and strategies to prevent HCC development are lacking. Aiming to discover therapeutic targets, we combined genome-wide transcriptomic analysis of liver tissues from patients with advanced liver disease and HCC and a cell-based system predicting liver disease progression and HCC risk. Computational analysis predicted peroxiredoxin 2 ( PRDX2 ) as a candidate gene mediating hepatocarcinogenesis and HCC risk. Analysis of tissues from patients with HCC confirmed a perturbed expression of PRDX2 in cancer. In vivo perturbation studies in mouse models for hepatocarcinogenesis driven by metabolic dysfunction–associated steatohepatitis showed that specific Prdx2 KO in hepatocytes improved metabolic liver functions, restored AMPK activity, and prevented HCC development by suppressing oncogenic signaling. Perturbation studies in HCC cell lines, a cell line–derived xenograft mouse model, and patient-derived HCC spheroids revealed that PRDX2 also mediates cancer initiation, cancer cell proliferation, and survival through its antioxidant activity. Targeting PRDX2 may therefore be a strategy to prevent HCC development in metabolic liver disease.