Aim and objective
Emerging translational evidence suggests that epigenetic alterations (DNA methylation, miRNA expression, and histone modifications) occur after external stimuli and may contribute ...to exacerbated inflammation and the risk of suffering several diseases including diabetes, cardiovascular diseases, cancer, and neurological disorders. This review summarizes the current knowledge about the harmful effects of high-fat/high-sugar diets, micronutrient deficiencies (folate, manganese, and carotenoids), obesity and associated complications, bacterial/viral infections, smoking, excessive alcohol consumption, sleep deprivation, chronic stress, air pollution, and chemical exposure on inflammation through epigenetic mechanisms. Additionally, the epigenetic phenomena underlying the anti-inflammatory potential of caloric restriction,
n
-3 PUFA, Mediterranean diet, vitamin D, zinc, polyphenols (i.e., resveratrol, gallic acid, epicatechin, luteolin, curcumin), and the role of systematic exercise are discussed.
Methods
Original and review articles encompassing epigenetics and inflammation were screened from major databases (including PubMed, Medline, Science Direct, Scopus, etc.) and analyzed for the writing of the review paper.
Conclusion
Although caution should be exercised, research on epigenetic mechanisms is contributing to understand pathological processes involving inflammatory responses, the prediction of disease risk based on the epigenotype, as well as the putative design of therapeutic interventions targeting the epigenome.
Obesity is a multifactorial disease characterized by an excessive weight for height due to an enlarged fat deposition such as adipose tissue, which is attributed to a higher calorie intake than the ...energy expenditure. The key strategy to combat obesity is to prevent chronic positive impairments in the energy equation. However, it is often difficult to maintain energy balance, because many available foods are high-energy yielding, which is usually accompanied by low levels of physical activity. The pharmaceutical industry has invested many efforts in producing antiobesity drugs; but only a lipid digestion inhibitor obtained from an actinobacterium is currently approved and authorized in Europe for obesity treatment. This compound inhibits the activity of pancreatic lipase, which is one of the enzymes involved in fat digestion. In a similar way, hundreds of extracts are currently being isolated from plants, fungi, algae, or bacteria and screened for their potential inhibition of pancreatic lipase activity. Among them, extracts isolated from common foodstuffs such as tea, soybean, ginseng, yerba mate, peanut, apple, or grapevine have been reported. Some of them are polyphenols and saponins with an inhibitory effect on pancreatic lipase activity, which could be applied in the management of the obesity epidemic.
Malnutrition is very prevalent in geriatric patients with hip fracture. Nevertheless, its importance is not fully recognized. The objective of this paper is to review the impact of malnutrition and ...of nutritional treatment upon outcomes and mortality in older people with hip fracture. We searched the PubMed database for studies evaluating nutritional aspects in people aged 70 years and over with hip fracture. The total number of studies included in the review was 44, which analyzed 26,281 subjects (73.5% women, 83.6 ± 7.2 years old). Older people with hip fracture presented an inadequate nutrient intake for their requirements, which caused deterioration in their already compromised nutritional status. The prevalence of malnutrition was approximately 18.7% using the Mini-Nutritional Assessment (MNA) (large or short form) as a diagnostic tool, but the prevalence was greater (45.7%) if different criteria were used (such as Body Mass Index (BMI), weight loss, or albumin concentration). Low scores in anthropometric indices were associated with a higher prevalence of complications during hospitalization and with a worse functional recovery. Despite improvements in the treatment of geriatric patients with hip fracture, mortality was still unacceptably high (30% within 1 year and up to 40% within 3 years). Malnutrition was associated with an increase in mortality. Nutritional intervention was cost effective and was associated with an improvement in nutritional status and a greater functional recovery. To conclude, in older people, the prevention of malnutrition and an early nutritional intervention can improve recovery following a hip fracture.
Obesity is often characterized by increased oxidative stress and exacerbated inflammatory outcomes accompanying infiltration of immune cells in adipocytes. The oxidative stress machinery and ...inflammatory signaling are not only interrelated, but their impairment can lead to an inhibition of insulin responses as well as a higher risk of cardiovascular diseases and associated features. Mitochondria, in addition to energy transformation, play a role in apoptosis, cellular proliferation, as well as in the cellular redox state control. Under certain circumstances, protons are able to re-enter the mitochondrial matrix via different uncoupling proteins, disturbing free radical production by mitochondria. Disorders of the mitochondrial electron transport chain, over-generation of reactive oxygen species, and lipoperoxides or alterations in antioxidant defenses have been reported in situations of obesity and type-2 diabetes. On the other hand, obesity has been linked to a low grade pro-inflammatory state, in which impairments in the oxidative stress and antioxidant mechanism could be involved. The current scientific evidence highlights the need of investigating the interplay between oxidative stress and inflammation with obesity/diabetes onset as well as the interactions of such factors either as a cause or consequence of obesity. The signaling mediated by the activation of inflammatory markers or nuclear factor kappa β and other transcription factors as central regulators of inflammation are key issues to understanding oxidative stress responses in obesity. This review aims at summarizing the main mechanisms and interplay factors between oxidative stress and inflammation in human obesity according to the last 10 years of research in the field.
Aging is a complex phenomenon characterized by the progressive loss of tissue and organ function. The oxidative-stress theory of aging postulates that age-associated functional losses are due to the ...accumulation of ROS-induced damage. Liver function impairment and non-alcoholic fatty liver disease (NAFLD) are common among the elderly. NAFLD can progress to non-alcoholic steatohepatitis (NASH) and evolve to hepatic cirrhosis or hepatic carcinoma. Oxidative stress, lipotoxicity, and inflammation play a key role in the progression of NAFLD. A growing body of evidence supports the therapeutic potential of omega-3 polyunsaturated fatty acids (n-3 PUFA), mainly docosahaexenoic (DHA) and eicosapentaenoic acid (EPA), on metabolic diseases based on their antioxidant and anti-inflammatory properties. Here, we performed a systematic review of clinical trials analyzing the efficacy of n-3 PUFA on both systemic oxidative stress and on NAFLD/NASH features in adults. As a matter of fact, it remains controversial whether n-3 PUFA are effective to counteract oxidative stress. On the other hand, data suggest that n-3 PUFA supplementation may be effective in the early stages of NAFLD, but not in patients with more severe NAFLD or NASH. Future perspectives and relevant aspects that should be considered when planning new randomized controlled trials are also discussed.
ABSTRACT
Diverse evidence suggests that the gut microbiota is involved in the development of obesity and associated comorbidities. It has been reported that the composition of the gut microbiota ...differs in obese and lean subjects, suggesting that microbiota dysbiosis can contribute to changes in body weight. However, the mechanisms by which the gut microbiota participates in energy homeostasis are unclear. Gut microbiota can be modulated positively or negatively by different lifestyle and dietary factors. Interestingly, complex interactions between genetic background, gut microbiota, and diet have also been reported concerning the risk of developing obesity and metabolic syndrome features. Moreover, microbial metabolites can induce epigenetic modifications (i.e., changes in DNA methylation and micro-RNA expression), with potential implications for health status and susceptibility to obesity. Also, microbial products, such as short-chain fatty acids or membrane proteins, may affect host metabolism by regulating appetite, lipogenesis, gluconeogenesis, inflammation, and other functions. Metabolomic approaches are being used to identify new postbiotics with biological activity in the host, allowing discovery of new targets and tools for incorporation into personalized therapies. This review summarizes the current understanding of the relations between the human gut microbiota and the onset and development of obesity. These scientific insights are paving the way to understanding the complex relation between obesity and microbiota. Among novel approaches, prebiotics, probiotics, postbiotics, and fecal microbiome transplantation could be useful to restore gut dysbiosis.
Adipose tissue releases bioactive mediators called adipokines. This review focuses on the effects of omentin, vaspin, cardiotrophin-1, Tumor necrosis factor-like Weak Inducer of Apoptosis (TWEAK) and ...nephroblastoma overexpressed (NOV/CCN3) on obesity and diabetes. Omentin is produced by the stromal-vascular fraction of visceral adipose tissue. Obesity reduces omentin serum concentrations and adipose tissue secretion in adults and adolescents. This adipokine regulates insulin sensitivity, but its clinical relevance has to be confirmed. Vaspin is produced by visceral and subcutaneous adipose tissues. Vaspin levels are higher in obese subjects, as well as in subjects showing insulin resistance or type 2 diabetes. Cardiotrophin-1 is an adipokine with a similar structure as cytokines from interleukin-6 family. There is some controversy regarding the regulation of cardiotrophin-1 levels in obese -subjects, but gene expression levels of cardiotrophin-1 are down-regulated in white adipose tissue from diet-induced obese mice. It also shows anti-obesity and hypoglycemic properties. TWEAK is a potential regulator of the low-grade chronic inflammation characteristic of obesity. TWEAK levels seem not to be directly related to adiposity, and metabolic factors play a critical role in its regulation. Finally, a strong correlation has been found between plasma NOV/CCN3 concentration and fat mass. This adipokine improves insulin actions.
BACKGROUND: The Mediterranean dietary pattern might be a potential tool for the prevention of obesity. OBJECTIVES: We studied the association between adherence to 6 previously published scores used ...to assess the adherence to the Mediterranean diet and weight change. We also assessed the risk of relevant weight gain (≥5 kg) or the risk of developing overweight or obesity. DESIGN: The study population included 10,376 Spanish men and women who were university graduates (mean age = 38 y) and were followed up for a mean (±SD) of 5.7 ± 2.2 y. Diet was assessed at baseline with a 136-item, previously validated food-frequency questionnaire. Weight was assessed at baseline and biennially during follow-up. RESULTS: Participants with the lowest adherence (less-than or equal to3 points) to the Mediterranean dietary score (MDS) proposed by Trichopoulou et al (range: 0-9; N Engl J Med 2003;348:2599-608) exhibited the highest average yearly weight gain, whereas participants with the highest (≥6 points) adherence exhibited the lowest weight gain (adjusted difference: -0.059 kg/y; 95% CI: -0.111, -0.008 kg/y; P for trend = 0.02). This inverse association was extended to other a priori-defined MDSs. The group with the highest adherence to the MDS also showed the lowest risk of relevant weight gain (≥5 kg) during the first 4 y of follow-up (odds ratio: 0.76; 95% CI: 0.64, 0.90). CONCLUSIONS: Adherence to the Mediterranean dietary pattern is significantly associated with reduced weight gain. This dietary pattern can be recommended to slow down age-related weight gain.
•Obese individuals have an increased risk to develop neurodegenerative diseases.•Obesity is usually accompanied by low-grade systemic inflammation.•Systemic and central inflammation may be a link ...between obesity and Alzheimer's disease.•Alteration in the microbiota-gut-brain axis may be involved in cognitive decline.•Antiinflammatory and antiobesity drugs could be useful in cognitive decline management.
Obesity prevalence is increasing steadily throughout the world's population in most countries and in parallel the prevalence of metabolic disorders including cardiovascular diseases and type 2 diabetes is also rising, but less is reported about excessive adiposity relationship with poorer cognitive performance, cognitive decline and dementia. Some human clinical studies have evidenced that obesity is related to the risk of the development of mild cognitive impairment, in the form of short-term memory and executive function deficits, as well as dementia and Alzheimer's disease. The precise mechanisms that underlie the connections between obesity and the risk of cognitive impairment are still largely unknown but potential avenues of further research include insulin resistance, the gut-brain axis, and systemic mediators and central inflammation processes. A common feature of metabolic diseases is a chronic and low-grade activation of the inflammatory system. This inflammation may eventually spread from peripheral tissue to the brain, and recent reports suggest that neuroinflammation is an important causal mechanism in cognitive decline. This inflammatory status could be triggered by changes in the gut microbiota composition. Consumption of diets high in fat and sugar influences the microbiota composition, which may lead to an imbalanced microbial population in the gut. Thus, it has recently been hypothesized that the gut microbiota could be part of a mechanistic link between the consumption of high fat and other unbalanced diets and impaired cognition, termed ‘gut-brain axis’. The present review will aim at providing an integrative analysis of the effects of obesity and unbalanced diets on cognitive performance and discusses some of the potential mechanisms involved, namely inflammation and changes in gut-brain axis. Moreover, the review aims to analyze anti-inflammatory drugs that have been tested for the treatment of cognition and obesity, recently approved anti-obesity drugs that could also have an impact on central nervous system, and bioactive food compounds that modulate gut microbiota and could have an impact through the gut-brain axis. In this era of precision nutrition medicine, it is imperative to identify the various metabolic-neurocognitive phenotypes in order to understand the processes that drive these diseases so that targeted therapeutic strategies to prevent and successfully manage these complex, multifactorial diseases could be designed and developed.
Dietary factors can affect telomere length (TL), a biomarker of aging, through oxidation and inflammation-related mechanisms. A Dietary Inflammatory Index (DII) could help to understand the effect of ...the inflammatory potential of the diet on telomere shortening.
This study aimed to determine the association of the DII with TL and to examine whether diet-associated inflammation could modify the telomere attrition rate after a 5-y follow-up of a Mediterranean dietary intervention.
This was a prospective study of 520 participants at high cardiovascular disease risk (mean ± SD age: 67.0 ± 6.0 y, 45% males) from the PREDIMED-NAVARRA (PREvención con DIeta MEDiterránea-NAVARRA) trial. Leukocyte TL was measured by quantitative real-time polymerase chain reaction at baseline and after 5 y of follow-up. The DII was calculated from self-reported data by using a validated 137-item food-frequency questionnaire.
Longer telomeres at baseline were found in participants who had a more anti-inflammatory diet (lowest DII score) (P-trend = 0.012). Longitudinal analyses further showed that a greater anti-inflammatory potential of the diet (i.e., a decrease in the DII) could significantly slow down the rate of telomere shortening. Moreover, the multivariable-adjusted OR for short telomeres (z score ≤20th percentile) was 1.80 (95% CI: 1.03, 3.17) in a comparison between the highest (proinflammatory) and the lowest (anti-inflammatory) DII tertiles. Similarly, a greater DII (greatest proinflammatory values) after a 5-y follow-up was associated with almost a 2-fold higher risk of accelerated telomere attrition compared with the highest decrease in DII (greatest anti-inflammatory values) during this period (P-trend = 0.025).
This study showed both cross-sectional and longitudinal associations between the inflammatory potential of the diet and telomere shortening in subjects with a high cardiovascular disease risk. Our findings are consistent with, but do not show, a beneficial effect of adherence to an anti-inflammatory diet on aging and health by slowing down telomere shortening. These results suggest that diet might play a key role as a determinant of TL through proinflammatory or anti-inflammatory mechanisms. This trial was registered at controlled-trials.com as ISRCTN35739639.
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