Obesity and overweight represent critical public health problems worldwide, driving the search for effective strategies for their prevention and treatment. Modulating appetite and satiety through natural compounds present in the diet emerges as a promising approach to controlling energy intake and improving metabolic balance. This article reviews the molecular and physiological mechanisms involved in appetite regulation, including the function of gastrointestinal hormones (GLP-1, CCK, PYY, ghrelin), the role of the hypothalamus, and the influence of microbial metabolites such as short-chain fatty acids (SCFAs). Different groups of compounds such as fibres, proteins, lipids, polyphenols, saponins, and alkaloids are analyzed in relation to their capacity to modulate both orexigenic (ghrelin) and anorexigenic signals (GLP-1, CCK, PYY), as well as their broader effects on neuroendocrine and metabolic pathways. Despite the growing body of preclinical evidence, results in humans are still limited and, at times, inconsistent, underscoring the need for long-term controlled studies to clarify their mechanisms and clinical potential. This review provides a comprehensive overview of the pathways through which dietary bioactive compounds can contribute to appetite regulation, providing a scientific basis for the development of nutritional interventions aimed at combating obesity and related metabolic disorders.

Sarcopenia, the progressive loss of skeletal muscle mass and function, represents a major public health concern due to its impact on mobility, independence, and quality of life, especially in oldadults. Current treatment strategies primarily rely on resistance training and nutritional support, with particular emphasis on adequate protein intake to stimulate muscle protein synthesis. In this review, we provide an overview of the pathophysiology of sarcopenia, with a focus on the molecular mechanisms underlying muscle atrophy and dysfunction. We explore the role of dietary protein as a cornerstone of sarcopenia management, highlighting current evidence on optimal protein sources and intake strategies. In addition, we examine other nutritional interventions, placing special emphasis on polyphenols, naturally occurring compounds known for their antioxidant and anti-inflammatory properties, which have shown promise in modulating pathways relevant to muscle preservation. Vitamin D and other nutritional supplements are also discussed in the context of their potential to support muscle health. Finally, we address emerging trends in the field, including targeting microbiota. By integrating current findings, this narrative review aims to provide a compilation of the evidence-based nutritional interventions for the prevention and management of sarcopenia.

ABSTRACT Omega-3 polyunsaturated fatty acids (n-3 PUFA) influence white adipose tissue (WAT) lipid buffering capacity; however, sex-specific regulation remains understudied. We recently reported that male mice fed a diet containing high alpha-linolenic acid (ALA) had increased WAT mass, reduced serum triglycerides and elevated lipolysis compared to mice fed a diet containing recommended levels of ALA, independent of background dietary protein. The current study examined whether subcutaneous and visceral WAT (scWAT, vWAT) lipolytic activity was altered in female C57BL/6N mice (n=16/group) fed low-ALA (1% energy) or high-ALA (3% energy) diets containing skim milk protein (SMP) or soy protein isolate (SPI) for 8 weeks. Body weight, WAT depot weights and serum triglycerides were unchanged in response to ALA content. Lipolytic markers were mostly unchanged by ALA content except for an increase in adipose triglyceride lipase (ATGL) in vWAT, while diets containing SPI modestly reduced serum cholesterol levels and increased total hormone-sensitive lipase (HSL) content in vWAT. Collectively, WAT lipolytic markers in female mice showed minimal response to diets containing high ALA content, unlike that previously reported in male mice. These results highlight the importance of considering both sexes to ensure generalizability of findings when investigating diet regulation of WAT lipid metabolism.

The age-related decrease in skeletal muscle mass and function, mostly known as sarcopenia, increases the risk of mobility impairments, chronic disease and early mortality. Physical activity and targeted dietary approaches are the most effective intervention to prevent or limit sarcopenia. Omega-3 polyunsaturated fatty acids (PUFA) could alleviate some aspects of age-related diseases. We investigated the effect of a chronic intake of a diet containing a high content of omega-3 PUFA in old mice exposed to a normocaloric or an obesogenic diet. Female C57BL/6J mice received a low-fat or a high-fat diet containing 5 or 6

Cachexia is a multifactorial syndrome that occurs in many cancers, particularly in their advanced stages, decreasing the quality of life and lifespan of patients. One of the hallmarks of cancer-associated cachexia is skeletal muscle wasting. Multiple causes include inflammation, metabolic deregulation, energy utilization, endoplasmic reticulum and oxidative stress. Loss of skeletal muscle is characterised by an imbalance in protein homeostasis, with decreased anabolism (regulated by the Akt/GSK3/eIF2α and Akt/mTORC1 pathways) and increased catabolism (regulated by autophagy and the ubiquitin-proteasome system), as well as an impairment in myogenesis. Accumulating evidence suggests that dietary intervention of β-hydroxybutyrate, the major ketone body produced by ketogenesis, and n-3 polyunsaturated fatty acids may mitigate skeletal muscle wasting. Polyunsaturated fatty acids and β-hydroxybutyrate are able to favourably modulate inflammation, insulin resistance, unfolded protein response and stresses (such as metabolic stress and oxidative stress). A well-adapted nutritional strategy may include a “classic” diet supplemented with β-hydroxybutyrate and polyunsaturated fatty acids to maintain skeletal muscle integrity and reduce wasting.

This study aimed at determining the effects of type II collagen (CII)-induced arthritis (CIA) on cardiac homeostasis in the contexts of a laboratory chow (LC) and a Western diet (WD). The influence of dietary docosahexaenoic acid (DHA) was also examined. Sixty female Wistar rats were assigned to five groups. The first two groups were fed the LC and were treated or not with CII (LC + CIA and LC); the third and fourth groups were fed a WD with or without CII treatment (WD + CIA and WD); and the fifth group was treated with CII and it was fed the WD whose 2.5

BACKGROUND:Sarcopenic obesity (SO) is a clinical condition defined by the coexistence of high body fat mass and low muscle function and mass, which increases the risk of adverse health outcomes, including disability and mortality. Early detection and frequent monitoring of SO are essential for preventive interventions and management strategies. The current binary approach for SO diagnosis is limited in capturing the spectrum of SO or its progression over time. The main objective of this study was to develop a continuous SOPi that integrates diagnostic criteria such as muscle function and body composition. We aimed to evaluate the association between SOPi and all-cause mortality, to identify baseline-related factors with SOPi and to assess changes in the SOPi over time. METHODS:Participants from the Rotterdam Study with baseline and follow-up measures of handgrip strength (HGS), dual-energy X-ray absorptiometry-measured appendicular lean mass index (ALM/kg) and body fat percentage (BF%) were included. SOPi was calculated as a sex-specific equation integrating z-scores (Z) of (BF%)-(HGS)-(ALM/kg). Cox regression and multivariable linear regression models were fitted to evaluate mortality risk and associated factors with SOPi, respectively. Subgroup analysis of SOPi changes was performed by linear mixed-effects models. RESULTS:In the total population (n = 5888, age 69.5 ± 9.1 years, BMI 27.5 ± 4.3 kg/m2, 56.8% females) and over the 9.9-year median follow-up period, 1538 (26.1%) participants died. Each standard deviation (SD) increase in sex-specific SOPi was associated with a 10% higher risk of premature death (HR = 1.10 [95%CI: 1.07; 1.13]). Thirteen factors were associated with high SOPi, such as reduced physical activity, higher triglyceride-glucose index, HOMA-IR, systemic inflammation, osteopenia, hypertension, liver steatosis, asthma, coronary heart disease, oral corticosteroid use, lower protein intake, lower quality of life and lower educational status. In participants with obesity, lower physical activity and/or insulin resistance (n = 1682), a significantly higher and faster increase in SOPi was observed compared to participants without these factors (males: β = 2.63 [95%CI: 2.22; 3.03]; females: β = 2.90 [95%CI: 2.58; 3.23]). CONCLUSION:SOPi is a significant predictor of premature death and can identify associated factors, particularly useful among persons at risk of SO. SOPi is higher and increases faster in individuals with specific phenotypes. SOPi integrates prognosis information, which could be used as a risk indicator and for prevention of SO.

White adipose tissue (WAT) is an endocrine organ essential for maintaining whole-body energy balance by regulating fatty acid uptake, storage, and release. Emerging evidence indicates that omega-3 fatty acids have a role in modulating WAT lipid metabolism. While most studies have focused on marine-derived omega-3s, considerably less is known about alpha-linolenic acid (ALA). Previous research suggests that ALA may prevent or restore impaired lipolysis in dysfunctional WAT. The primary objective of this study was to examine the effects of ALA on WAT lipolytic activity and whether this varied with background dietary protein. Male C57BL/6N mice (n=16/group) were fed moderate-fat diets containing either 1% (low-ALA) or 3% (high-ALA) energy from ALA (provided by flaxseed oil), and either skim milk protein or a soy protein isolate for 8 weeks. Mice fed high-ALA diets showed increased body weight gain and WAT depot weights, reduced serum triglycerides, and increased serum glycerol levels. The higher serum glycerol levels in high-ALA fed mice were reflected in higher glycerol release from cultured adipose tissue explants stimulated with a β-adrenergic agonist. Markers of WAT lipolysis, including ATGL and phosphorylated HSL, were either lower or unchanged in mice fed high-ALA diets. Background dietary protein (from either dairy or soy) had little-to-no-effect on study endpoints. Our data suggests that increased dietary ALA intake improves circulating TAG levels while reducing markers of lipolysis in WAT depots. The increase in glycerol observed with high-ALA intake may point to a potential regulation of WAT glycerogenesis and/or aquaporin expression that warrants future investigation.

Addressing the physiological effects of bioactive compounds in metabolic diseases (i.e., obesity, diabetes, liver steatosis) and establishing their mechanisms of action have been a major interest for the last decades. However, methodologies that can be applied to achieve this can vary greatly, leading to a limited type of information. Thus, the accuracy, robustness, reliability and potential (human) translation are highly reliant on the experimental design and selected methodological models. This review presents an update exploring the main features, advantages and disadvantages of most important pre-clinical models used at the present time to study the effects of bioactive compounds on metabolic diseases. Moreover, future challenges in developing new methods are also depicted. In vitro models (enzyme assays and standard two-dimensional cultures of adipocytes, skeletal muscle cells) are intrinsically well established and constitute the first choice and most widely used methods to study bioactive compounds in metabolic diseases. However, novel models such as three-dimensional cultures (spheroids, organoids) are also starting to emerge and complement traditional culture systems. Models of small organisms (C. elegans, D. melanogaster) and non-mammal vertebrates (D. rerio) represent a scientific advantage and a middle-step before traditional mammalian models (rats and mice). This article provides extensive information and a critical overview of a wide range of methods that represent present and future avenues towards a further understanding of metabolic diseases. Combining and developing new methods will be key for future progression on the effects of bioactive compounds on metabolic diseases, as well as to minimize the use of mammalian models due to ethical reasons.

Importance:Sarcopenia and obesity are 2 global concerns associated with adverse health outcomes in older people. Evidence on the population-based prevalence of the combination of sarcopenia with obesity (sarcopenic obesity [SO]) and its association with mortality are still limited. Objective:To investigate the prevalence of sarcopenia and SO and their association with all-cause mortality. Design, Setting, and Participants:This large-scale, population-based cohort study assessed participants from the Rotterdam Study from March 1, 2009, to June 1, 2014. Associations of sarcopenia and SO with all-cause mortality were studied using Kaplan-Meier curves, Cox proportional hazards regression, and accelerated failure time models fitted for sex, age, and body mass index (BMI). Data analysis was performed from January 1 to April 1, 2023. Exposures:The prevalence of sarcopenia and SO, measured based on handgrip strength and body composition (BC) (dual-energy x-ray absorptiometry) as recommended by current consensus criteria, with probable sarcopenia defined as having low handgrip strength and confirmed sarcopenia and SO defined as altered BC (high fat percentage and/or low appendicular skeletal muscle index) in addition to low handgrip strength. Main Outcome and Measure:The primary outcome was all-cause mortality, collected using linked mortality data from general practitioners and the central municipal records, until October 2022. Results:In the total population of 5888 participants (mean [SD] age, 69.5 [9.1] years; mean [SD] BMI, 27.5 [4.3]; 3343 [56.8%] female), 653 (11.1%; 95% CI, 10.3%-11.9%) had probable sarcopenia and 127 (2.2%; 95% CI, 1.8%-2.6%) had confirmed sarcopenia. Sarcopenic obesity with 1 altered component of BC was present in 295 participants (5.0%; 95% CI, 4.4%-5.6%) and with 2 altered components in 44 participants (0.8%; 95% CI, 0.6%-1.0%). An increased risk of all-cause mortality was observed in participants with probable sarcopenia (hazard ratio [HR], 1.29; 95% CI, 1.14-1.47) and confirmed sarcopenia (HR, 1.93; 95% CI, 1.53-2.43). Participants with SO plus 1 altered component of BC (HR, 1.94; 95% CI, 1.60-2.33]) or 2 altered components of BC (HR, 2.84; 95% CI, 1.97-4.11) had a higher risk of mortality than those without SO. Similar results for SO were obtained for participants with a BMI of 27 or greater. Conclusions and Relevance:In this study, sarcopenia and SO were found to be prevalent phenotypes in older people and were associated with all-cause mortality. Additional alterations of BC amplified this risk independently of age, sex, and BMI. The use of low muscle strength as a first step of both diagnoses may allow for early identification of individuals at risk for premature mortality.

En raison de son expansion au cours de l’obésité, le tissu adipeux blanc subit des modifications structurales et fonctionnelles, contribuant à l’élévation du risque de développer un diabète et des maladies cardiovasculaires, et à une mortalité précoce. Cependant, des travaux suggèrent que la qualité nutritionnelle de certains nutriments énergétiques peut moduler la réponse physiologique en situation de balance énergétique positive. En effet, la qualité des acides gras alimentaires peut moduler de nombreuses fonctions biologiques et contribuer à ralentir ou prévenir certaines pathologies. Des études ont mis en évidence l’intérêt des acides gras polyinsaturés oméga-3 pour la santé, en particulier concernant les fonctions du tissu adipeux blanc associées à l’obésité et à ses comorbidités. Cet intérêt est d’autant plus pertinent au vu des modifications des profils des régimes alimentaires en acides gras, qui ont pu contribuer à l’explosion de la prévalence de l’obésité dans les sociétés occidentales. Cet article décrit comment les oméga-3 peuvent influencer l’accumulation et la fonction du tissu adipeux blanc. Pour cela, il s’appuie sur des données observationnelles chez l’homme, des interventions cliniques ou précliniques, ainsi que sur des modèles cellulaires.

As a result of its expansion during obesity, white adipose tissue undergoes structural and functional changes that contribute to an increased risk of developing diabetes or cardiovascular disease, and premature death. Compelling evidence suggests that the quality of some energy nutrients can modulate the physiological response to a positive energy balance. Indeed, the quality of dietary fatty acids can modulate numerous biological functions and slow down or prevent some pathologies. Studies have highlighted the health benefits of omega-3 polyunsaturated fatty acids, particularly regarding adipose tissue functions during obesity and against related co-morbidities. In connection with changes in the fatty acid profile of diets that may have contributed to the rise in obesity prevalence in Western countries, this article describes how omega-3s can modulate the accumulation and function of the adipose tissue. It was prepared based on human observational data, preclinical and clinical intervention data, and cellular models. (c) 2024 Societe franc,aise de nutrition. Published by Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Myosteatosis occurs in response to excess circulating fatty acids and is associated with muscle dysfunction. This study aimed to characterize the sequence of events of lipid-induced toxicity within muscle cells and the role of polyunsaturated fatty acids (PUFA) as potential preventive factors. Myosteatosis was induced in C2C12 myotubes exposed to palmitic acid (PAL 500µM). Furthermore, cells were co-incubated with PUFA (α-linolenic acid = ALA, Eicosapentaenoic acid = EPA, Docosahexaenoic acid = DHA; Arachidonic acid = ARA) over a period of 48 h. Cell viability, morphology, and measures of lipid and protein metabolism were assessed at 6, 12, 24, and 48 h. We observed that myotube integrity was rapidly and progressively disrupted by PAL treatment after 12 h, ultimately leading to cell death (41.7% cell survival at 48 h, p < .05). Cell death did not occur in cells exposed to PAL+ARA and PAL+DHA. After 6 h of PAL treatment, an accumulation of large lipid droplets was observed within the cell (6 folds, p < .05). This was associated with an increase in ceramides (CER x3 fold change) and diacylglycerol (DAG x150 fold change) contents (p < .05). At the same time, insulin was no longer able to stimulate protein synthesis (p < .05) nor leverage autophagic flux (p < .05). DHA and ARA were able to completely reverse the defect in protein synthesis and partially modulate the accumulation of CER and DAG. These findings present new and intriguing research avenues in the field of muscle metabolism and nutrition, particularly in the context of aging, chronic muscle disorders, and insulin resistance.

Background: There is a myriad of metabolic roles of omega-3 fatty acids. More recently, studies have looked at omega-3 fatty acids effects on skeletal muscle. Objectives: The objective was to determine their effects in situations such as physical activity, obesity, sarcopenia and cachexia. Methods: Bibliographic searches focused on the PubMed database, looking in priority at systematic reviews, until November 2023. Twenty-seven papers were finally included. Results: Omega-3 fatty acids could increase protein anabolism, reduce protein catabolism in the context of exercise-related muscle damages, and could induce beneficial mitochondrial modifications. In obesity, omega-3 fatty acids participate in weight loss and its maintenance, and can help decrease insulin resistance. In sarcopenia atrophic conditions, omega 3 fatty acids allow muscle mass and function maintenance. In cancer cachexia, omega 3 fatty acids are more efficient at the pre-cachectic stage, as they can reduce protein catabolism and increase protein anabolism, but cannot reverse energy imbalance. Conclusions: Omega 3 fatty acids have multiple beneficial effects on skeletal muscle in physical activity, obesity, sarcopenia and cachexia. Yet, these effects are mediated by EPA and DHA, whose sources are solely of marine origins. As marine resources are overexploited, finding diverse sources of omega-3 fatty acids is crucial.

This Special Issue of the Journal of Physiology and Biochemistry contains 7 contributions that have been elaborated in the context of the mini-network “Consortium of Trans-Pyrenean Investigations on Obesity and Diabetes” (CTPIOD), which is on its 19th year of existence. This scientific community, mostly involving research groups from France and Spain, but also open to participants coming from other countries, is focused on investigating the molecular and physiological mechanisms implicated in the development of obesity, diabetes, non-alcoholic fatty liver disease, and other noncommunicable diseases, as well as new preventive and therapeutic strategies. This special issue covers novel nutritional, molecular, and physiological aspects related to these metabolic diseases. Some of these papers emerge from the lectures of the 19th Conference on Trans-Pyrenean Investigations in Obesity and Diabetes, organized by the University of Zaragoza and celebrated in the town of Jaca (Spain) on 17-18th October 2022, and have been prepared in collaboration between different groups of the network. Many lectures were focused on the preventive role of specific fatty acids, dietary phenolic compounds and other phytochemicals against metabolic disorders. Consequently, we encouraged submission of original research in this field for this special issue.

TRUEFAD (TRUE Fiber Atrophy Distinction) is a bioimagery user-friendly tool developed to allow consistent and automatic measurement of myotube diameter in vitro, muscle fiber size and type using rodents and human muscle biopsies. This TRUEFAD package was set up to standardize and dynamize muscle research via easy-to-obtain images run on an open-source plugin for FIJI. We showed here both the robustness and the performance of our pipelines to correctly segment muscle cells and fibers. We evaluated our pipeline on real experiment image sets and showed consistent reliability across images and conditions. TRUEFAD development makes possible systematical and rapid screening of substances impacting muscle morphology for helping scientists focus on their hypothesis rather than image analysis.

Previous studies in Western diet (WD)-fed male rats have highlighted a link between the stimulation of cardiac contractility, mitochondrial adaptations and a pro-inflammatory fatty acid profile of phospholipids in the heart. Our objectives were to determine (1) if WD-fed female Wistar rats and obese humans display a similar pro-inflammatory profile in their cardiac phospholipids and (2) if this lipid profile is associated with deleterious effects on the heart of the female rodents. Female Wistar rats were fed WD for 5 weeks or a laboratory chow as a control. Ionic homeostasis, redox status, inflammation markers, and fatty acid composition of phospholipids were analysed in the heart. WD increased the abdominal fat mass without modifying the body weight of female rats. As previously found in males, a WD induced a shift in membrane fatty acid composition toward a pro-inflammatory profile in the female rats, but not in obese humans. It was associated with an increased COX2 expression suggesting an increased pro-inflammatory eicosanoid production. Signs of increased intracellular calcium strongly supported a stimulation of cardiac contractility without any induction of apoptosis. The heart of WD-fed rats exhibited a hypoxic state as a higher HIF1-α expression was reported. The expressions of antioxidant enzymes were increased, but the redox reserves against reactive oxygen species were lowered. In conclusion, as previously observed in males, we suppose that cardiac abnormalities are magnified with severe obesity in female rats, leading to hypoxia and intense oxidative stress which could ultimately induce cell death and heart failure.

Sarcopenic obesity (SO) is defined as the combination of excess fat mass (obesity) and low skeletal muscle mass and function (sarcopenia). The identification and classification of factors related to SO would favor better prevention and diagnosis. the present article aimed to (i) define a list of factors related with SO based on literature analysis, (ii) identify clinical conditions linked with SO development from literature search and (iii) evaluate their relevance and the potential research gaps by consulting an expert panel.From 4746 articles screened, 240 articles were selected for extraction of the factors associated with SO. Factors were classified according to their frequency in the literature. Clinical conditions were also recorded. Then, they were evaluated by a panel of expert for evaluation of their relevance in SO development. Experts also suggested additional factors.Thirty-nine unique factors were extracted from the papers and additional eleven factors suggested by a panel of experts in the SO field. The frequency in the literature showed insulin resistance, dyslipidemia, lack of exercise training, inflammation and hypertension as the most frequent factors associated with SO whereas experts ranked low spontaneous physical activity, protein and energy intakes, low exercise training and aging as the most important.Although literature and expert panel presented some differences, this first list of associated factors could help to identify patients at risk of SO. Further work is needed to confirm the contribution of factors associated with SO among the population overtime or in randomized controlled trials to demonstrate causality.

AIMS:Rheumatoid arthritis is an autoimmune disease which induces chronic inflammation and increases the risk for sarcopenia and metabolic abnormalities. Nutritional strategies using omega 3 polyunsaturated fatty acids could be proposed to alleviate inflammation and improve the maintenance of lean mass. Independently, pharmacological agents targeting key molecular regulators of the pathology such as TNF alpha could be proposed, but multiple therapies are frequently necessary increasing the risk for toxicity and adverse effects. The aim of the present study was to explore if the combination of an anti-TNF therapy (Etanercept) with dietary supplementation with omega 3 PUFA could prevent pain and metabolic effects of RA.MATERIALS AND METHODS:RA was induced using collagen-induced arthritis (CIA) in rats to explore of supplementation with docosahexaenoic acid, treatment with etanercept or their association could alleviate symptoms of RA (pain, dysmobility), sarcopenia and metabolic alterations.KEY FINDINGS:We observed that Etanercept had major benefits on pain and RA scoring index. However, DHA could reduce the impact on body composition and metabolic alterations.SIGNIFICANCE:This study revealed for the first time that nutritional supplementation with omega 3 fatty acid could reduce some symptoms of rheumatoid arthritis and be an effective preventive treatment in patients who do not need pharmacological therapy, but no sign of synergy with an anti-TNF agent was observed.

Overtraining syndrome is a condition resulting from excessive training load associated with inadequate recovery and poor sleep quality, leading to performance decrements and fatigue. Here we hypothesized that vitamin D (VitD) deficiency is a lead factor in the development of the overtraining syndrome. To test this hypothesis, two groups of 60‐week‐old C57BL/6 mice followed a 16‐week excessive eccentric‐based overtraining by excessive downhill running with or without dietary VitD depletion (EX and EX‐D− groups). Two control groups were trained by uphill running at the same load with or without VitD depletion (CX and CX‐D− groups). Handgrip strength decreased throughout the protocol for all groups but the decrease was sharper in EX‐D− group (VitD × training, p = 0.0427). At the end of the protocol, the mass of Triceps brachii muscle, which is heavily stressed by eccentric contractions, was reduced in eccentric‐trained groups (training effect, p = 0.0107). This atrophy was associated with a lower concentration of the anabolic myokine IL‐15 (training effect, p = 0.0314) and a tendency to a higher expression of the atrogene cathepsin‐L (training effect, p = 0.0628). VitD depletion led to a 50% decrease of the fractional protein synthesis rate in this muscle (VitD effect, p = 0.0004) as well as decreased FGF21 (VitD effect, p = 0.0351) and increased osteocrin (VitD effect, p = 0.038) concentrations that would lead to metabolic defects. Moreover, the proportion of anti‐inflammatory Th2 lymphocytes was significantly decreased by the combination of eccentric training with VitD depletion (vitD × training, p = 0.0249) suggesting a systemic inflammation. Finally, exploratory behavior time of mice was decreased by VitD depletion (VitD effect, p = 0.0146) suggesting a cognitive dysfunction. Our results suggest that VitD deficiency exacerbates the effects of overtraining.