Gut microbiota (GM) is a key contributor to host metabolism and physiology. Data generated on comparing diseased and healthy subjects have reported changes in the GM profile between both health ...states, suggesting certain bacterial composition could be involved in pathogenesis. Moreover, studies reported that reshaping of GM could contribute actively to disease recovery. Interestingly, ketogenic diets (KD) have emerged recently as new economic dietotherapeutic strategy to combat a myriad of diseases (refractory epilepsy, obesity, cancer, neurodegenerative diseases…). KD, understood in a broad sense, refers to whatever dietetic approximation, which causes physiological ketosis. Therefore, high fat-low carbs diets, fasting periods or caloric restriction constitute different strategies to produce an increase of main ketones bodies, acetoacetate and β-hydroxybutyrate, in blood. Involved biological mechanisms in ketotherapeutic effects are still to be unravelled. However, it has been pointed out that GM remodelling by KD, from now on “keto microbiota”, may play a crucial role in patient response to KD treatment. In fact, germ-free animals were resistant to ketotherapeutic effects; reinforcing keto microbiota may be a powerful contributor to host disease recovery. In this review, we will comment the influence of gut microbiota on host, as well as, therapeutic potential of ketogenic diets and keto microbiota to restore health status. Current progress and limitations will be argued too. In spite of few studies have defined applicability and mechanisms of KD, in the light of results, keto microbiota might be a new useful therapeutic agent.
DNA damage has been extensively studied as a potentially helpful tool in assessing and preventing cancer, having been widely associated with the deregulation of DNA damage repair (DDR) genes and with ...an increased risk of cancer. Adipose tissue and tumoral cells engage in a reciprocal interaction to establish an inflammatory microenvironment that enhances cancer growth by modifying epigenetic and gene expression patterns. Here, we hypothesize that 8-oxoguanine DNA glycosylase 1 (OGG1)-a DNA repair enzyme-may represent an attractive target that connects colorectal cancer (CRC) and obesity. In order to understand the mechanisms underlying the development of CRC and obesity, the expression and methylation of DDR genes were analyzed in visceral adipose tissue from CRC and healthy participants. Gene expression analysis revealed an upregulation of
expression in CRC participants (
< 0.005) and a downregulation of
in normal-weight healthy patients (
< 0.05). Interestingly, the methylation analysis showed the hypermethylation of
in CRC patients (
< 0.05). Moreover, expression patterns of
were found to be regulated by vitamin D and inflammatory genes. In general, our results showed evidence that
can regulate CRC risk through obesity and may act as a biomarker for CRC.
Vitamin D, microbiota, and the Mediterranean diet (MedDiet) have been the focus of recent research due to their potential role in maintaining overall health. We hypothesize that MedDiet may alter the ...gut microbiota profile through changes in vitamin D levels. We aimed to investigate changes in gut microbiota and serum vitamin D levels after a MedDiet within a lifestyle intervention. The study included 91 patients with obesity and metabolic syndrome, who were categorized based on their serum vitamin D levels as having either optimal or low 25-hydroxyvitamin D 25(OH)D levels. The profile of the gut microbiota was analyzed by the 16S rRNA sequencing, inferring its functionality through PICRUsT. Participants underwent a hypocaloric MedDiet and change in their lifestyle for 1 year, and the profile and functionality of their gut microbiota were evaluated by analyzing inter-individual differences in time. At baseline, gut microbiota profiles qualitatively differed between participants with Optimal or Low 25(OH)D levels Unweighted (p = 0.016). Moreover, participants with Optimal 25(OH)D levels showed a higher gut microbiota diversity than those with Low 25(OH)D levels (p < 0.05). The differential analysis of abundance between the Low and Optimal 25(OH)D groups revealed differences in the levels of Bacteroides, Prevotella, and two Clostridiales features. After 1-year dietary intervention, both groups increased their 25(OH)D levels. Furthermore, both groups did not show significant differences in gut microbiota diversity, although the Low 25(OH)D group showed greater improvement in gut microbiota diversity by comparing at baseline and after dietary intervention (p < 0.05). Changes in specific bacterial taxa were observed within each group but did not differ significantly between the groups. Metabolic pathway analysis indicated differences in microbial functions between the groups (p < 0.05). These findings suggest that 25(OH)D status is associated with gut microbiota composition, diversity, and functionality, and lifestyle intervention can modulate both gut microbiota and 25(OH)D levels, potentially influencing metabolic pathways.
Purpose of Review
Metabolic and bariatric surgery (MBS) is considered to be the most effective treatment for obesity. Not only due to the significant weight reduction but also because of the many ...health benefits associated with it. In the last 5 years, several studies have suggested that epigenetic modifications could be involved in the mechanisms underlying the response to bariatric surgery. In this review, we will compile the different studies (2012–2017) concerning the effect of this surgical procedure on DNA methylation patterns (the most studied epigenetic marker) and its association with metabolic improvement. This is an emerging area, and currently, there are not many studies in the literature. The aim is to show what has been done so far and what the future direction in this emerging area might be.
Recent Findings
Recent findings have shown how metabolic and bariatric surgery modifies the DNA methylation profile of the specific genes associated with the pathophysiology of the disease. The studies were performed in morbidly obese subjects, mainly in women, with the aim of reducing weight and improving the obesity-associated comorbidities. DNA methylation has been measured both in specific tissue and in peripheral blood samples. In general, studies about site-specific DNA methylation have shown a change in the methylation profile after surgery, whereas the studies analyzing global DNA methylation are not so conclusive.
Summary
Summing up, metabolic and bariatric surgery can modify the DNA methylation profile of different genes and contributes to the metabolic health benefits that are often seen after metabolic and bariatric surgery. Although there are still many issues to be resolved, the capacity to revert the DNA methylation profile of specific sites opens a window for searching for target markers to treat obesity-related comorbidities.
The PPAR nuclear receptor family has acquired great relevance in the last decade, which is formed by three different isoforms (PPARα, PPAR β /δ, and PPAR ϒ). Those nuclear receptors are members of ...the steroid receptor superfamily which take part in essential metabolic and life-sustaining actions. Specifically, PPARG has been implicated in the regulation of processes concerning metabolism, inflammation, atherosclerosis, cell differentiation, and proliferation. Thus, a considerable amount of literature has emerged in the last ten years linking PPARG signalling with metabolic conditions such as obesity and diabetes, cardiovascular disease, and, more recently, cancer. This review paper, at crossroads of basic sciences, preclinical, and clinical data, intends to analyse the last research concerning PPARG signalling in obesity and cancer. Afterwards, possible links between four interrelated actors will be established: PPARG, the vitamin D/VDR system, obesity, and cancer, opening up the door to further investigation and new hypothesis in this fascinating area of research.
Backgrounds
Vitamin D and testosterone deficiency have been widely related to obesity. However, only a few studies have investigated the effect of vitamin D on testosterone in the context of obesity, ...in which controversial results have been raised.
Objectives
The purpose of this study was to determine the relationship between serum 25-hydroxyvitamin D (25(OH)D) and testosterone levels in young men with different grade of obesity.
Design and methods
This cross-sectional study included 269 healthy young men with obesity (body mass index (BMI) ≥ 30 kg/m
2
). Participants were divided into two groups based on their serum 25(OH)D levels (134 subjects with vitamin D sufficiency and 135 participants with vitamin D deficiency, according to the 50
th
percentile of 25(OH)D). Serum 25(OH)D and sex hormones have been measured. The relationships between 25(OH)D, sex hormones, and obesity grades were investigated with linear and binary logistic regression analyses, as well as mediation analysis.
Results
Compared to the 25(OH)D sufficiency group, total and free testosterone levels were found to be decreased, whereas serum androstenedione levels were increased in the 25(OH)D deficiency group (
p
<0.05). Using multivariable lineal regression analyses, 25(OH)D was correlated with the majority of sex hormones (
p
<0.05). When mediation with BMI was performed, the direct effect between 25(OH)D and sex hormones disappeared, and only the indirect effect
via
BMI remained (demonstrating the importance of BMI). Furthermore, after controlling for age and smoking status, we discovered that total testosterone and SHBG were both significantly associated with 25(OH)D (
p
<0.05) in subjects with obesity type III. Using a mediation analysis, we discovered that BMI had a partial effect on the association between 25(OH)D and total testosterone levels in morbidly obese participants, indicating that a direct association between 25(OH)D and total testosterone levels, and that BMI partially mediated this association.
Conclusions
Serum 25(OH)D is associated with total testosterone levels in only those subjects with morbid obesity, suggesting a specific benefit in severe cases of obesity. Additional research is needed to elucidate possible common mechanisms.
In the last two decades vitamin D (VD) research has demonstrated new extraskeletal actions of this pre-hormone, suggesting a protective role of this secosteroid in the onset, progression and ...prognosis of several chronic noncommunicable diseases, such as cardiovascular disease, diabetes mellitus or cancer.
Regarding carcinogenesis, both preclinical and epidemiological evidence available show oncoprotective actions of VD and its receptor, the VDR. However, in late neoplastic stages the VD system (VDS) seems to be less functional, which appears to be due to an epigenetic silencing of the system. In preclinical experimental studies, VD presents oncoprotective actions through modulation of inflammation, cell proliferation, cell differentiation, angiogenesis, invasive and metastatic potential, apoptosis, miRNA expression regulation and modulation of the Hedgehog signalling pathway. Moreover, epidemiological evidence points towards an oncoprotective role of vitamin D and VDR in colorectal cancer. This association is more controversial with breast, ovarian and prostate cancers, although with a few adverse effects. Nonetheless, we should consider other factors to determine the benefit of increased serum concentration of VD. Much of the epidemiological evidence is still inconclusive, and we will have to wait for new, better-designed ongoing RCTs and their results to discern the real effect of vitamin D in cancer risk reduction and therapy.
The objective of this literature review is to offer an up-to-date analysis of the role of the VD and VDR, in the onset, progression and prognosis of all types of cancer. We further discuss the available literature and suggest new hypotheses and future challenges in the field of VD research.
BACKGROUND AND PURPOSE Peripheral blockade of cannabinoid CB1 receptors has been proposed as a safe and effective therapy against obesity, putatively devoid of the adverse psychiatric side effects of ...centrally acting CB1 receptor antagonists. In this study we analysed the effects of LH‐21, a peripherally acting neutral cannabinoid receptor antagonist with poor brain penetration, in an animal model of diet‐induced obesity.
EXPERIMENTAL APPROACH To induce obesity, male Wistar rats were fed a high‐fat diet (HFD; 60 kcal% fat) whereas controls received a standard diet (SD; 10 kcal% fat). Following 10 weeks of feeding, animals received a daily i.p. injection of vehicle or 3 mg·kg−1 LH‐21 for 10 days. Plasma and liver samples were used for biochemical analyses whereas visceral fat‐pad samples were analysed for lipid metabolism gene expression using real‐time RT‐PCR. In addition, the potential of LH‐21 to interact with hepatic cytochrome P450 isoforms and cardiac human Ether‐à‐go‐go Related Gene (hERG) channels was evaluated.
KEY RESULTS LH‐21 reduced feeding and body weight gain in HFD‐fed animals compared with the control group fed SD. In adipose tissue, this effect was associated with decreased gene expression of: (i) leptin; (ii) lipogenic enzymes, including SCD‐1; (iii) CB1 receptors; and (iv) both PPARα and PPARγ. Although there were no significant differences in plasma parameters between HFD‐ and SD‐fed rats, LH‐21 did not seem to induce hepatic, cardiac or renal toxicity.
CONCLUSIONS AND IMPLICATIONS These results support the hypothesis that treatment with the peripherally neutral acting CB1 receptor antagonist, LH‐21, may promote weight loss through modulation of visceral adipose tissue.
The World Health Organization (WHO) considers that obesity has reached proportions of pandemic. Experts also insist on the importance of considering obesity as a chronic disease and one of the main ...contributors to the worldwide burden of other nontransmissible chronic diseases, which have a great impact on health, lifestyle, and economic cost. One of the most current challenges of biomedical science faces is to understand the origin of the chronic nontransmissible diseases, such as obesity and cancer. There is a large evidence, both in epidemiological studies in humans and in animal models, of the association between obesity and an increased risk of cancer incidence. In the last years, the initial discovery of epigenetic mechanisms represents the most relevant finding to explain how the genome interacts with environmental factors and the ripple effects on disease pathogeneses. Since then, all epigenetic process has been investigated by the scientific communities for nearly two decades to determine which components are involved in this process. DNA/RNA methylation and miRNA are classified as two of the most important representative classes of such epigenetic mechanisms and dysregulated activity of such mechanism can certainly contribute to disease pathogenesis and/or progression especially in tumors. This review article serves to highlight the impact of DNA/RNA methylation and miRNA-based epigenetic mechanism activities in the interplay between obesity and the development and clinical significance of colorectal cancer.
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