TLR9 in MAFLD and NASH: At the Intersection of Inflammation and Metabolism.

Toll-Like Receptor 9 (TLR9) is an ancient receptor integral to the primordial functions of inflammation and metabolism. TLR9 functions to regulate homeostasis in a healthy system under acute stress. The literature supports that overactivation of TLR9 under the chronic stress of obesity is a critical driver of the pathogenesis of NASH and NASH-associated fibrosis. Research has focused on the core contributions of the parenchymal and non-parenchymal cells in the liver, adipose, and gut compartments. TLR9 is activated by endogenous circulating mitochondrial DNA (mtDNA). Chronically elevated circulating levels of mtDNA, caused by the stress of overnutrition, are observed in obesity, metabolic dysfunction-associated fatty liver disease (MAFLD), and NASH. Clinical evidence is supportive of TLR9 overactivation as a driver of disease. The role of TLR9 in metabolism and energy regulation may have an underappreciated contribution in the pathogenesis of NASH. Antagonism of TLR9 in NASH and NASH-associated fibrosis could be an effective therapeutic strategy to target both the inflammatory and metabolic components of such a complex disease.

Precision Nutrition and the Microbiome Part II: Potential Opportunities and Pathways to Commercialisation.

Modulation of the human gut microbiota through probiotics, prebiotics and dietary fibre are recognised strategies to improve health and prevent disease. Yet we are only beginning to understand the impact of these interventions on the gut microbiota and the physiological consequences for the human host, thus forging the way towards evidence-based scientific validation. However, in many studies a percentage of participants can be defined as 'non-responders' and scientists are beginning to unravel what differentiates these from 'responders;' and it is now clear that an individual's baseline microbiota can influence an individual's response. Thus, microbiome composition can potentially serve as a biomarker to predict responsiveness to interventions, diets and dietary components enabling greater opportunities for its use towards disease prevention and health promotion. In Part I of this two-part review, we reviewed the current state of the science in terms of the gut microbiota and the role of diet and dietary components in shaping it and subsequent consequences for human health. In Part II, we examine the efficacy of gut-microbiota modulating therapies at different life stages and their potential to aid in the management of undernutrition and overnutrition. Given the significance of an individual's gut microbiota, we investigate the feasibility of microbiome testing and we discuss guidelines for evaluating the scientific validity of evidence for providing personalised microbiome-based dietary advice. Overall, this review highlights the potential value of the microbiome to prevent disease and maintain or promote health and in doing so, paves the pathway towards commercialisation.

[Is the individual motivational interviewing effective in overweight and obesity treatment? A systematic review]. / ¿Es efectiva la entrevista motivacional individual en la malnutrición por exceso? Una revisión sistemática de la literatura.

OBJECTIVE: To analyze the effectiveness of individual motivational interviewing (MI) in the ambulatory treatment of the overweight and obese. DESIGN: The protocol of this systematic review is registered in PROSPERO N° CDR42017058814. DATABASES: EBSCO-CINAHL, Pubmed, Scielo, PsycoINFO from 2010 to 2017. STUDY SELECTION: We included studies with overweight and obese adult participants, randomized trial and case control studies, with MI being applied individually and face to face, with primary or secondary results in changes in body composition (weight or BMI), published in English or Spanish, with available text and in peer-reviewed journals. DATA EXTRACTION: We obtained anthropometric, behavioral, psychosocial, and other variables as effects of MI. In addition, we collected descriptive variables of the interventions. RESULTS: Eleven articles were included in this revision. There is a great variability between the studies in terms of population, kind of intervention, and time of follow-up. In most of them, some effect was observed in reducing bodyweight, reaching a maximum of 7kg in the group that received the MI. There are positive variations in psychosocial and metabolic variables in the studies. CONCLUSIONS: Individual MI interventions have a modest effect on the variation of bodyweight, and could have a positive impact on behavioral, psychosocial, and other variables. More studies are needed to elucidate the best form of MI application with regard to effectiveness on different variables. The primary healthcare system is in an advantageous position for generating fruitful research on this motivational strategy.

The effects of different forms of daily exercise on metabolic function following short-term overfeeding and reduced physical activity in healthy young men: study protocol for a randomised controlled trial.

BACKGROUND: Short-term overfeeding combined with reduced physical activity impairs metabolic function and alters the expression of key genes within adipose tissue. We have shown that daily vigorous-intensity running can prevent these changes independent of any net effect on energy imbalance. However, which type, intensity and/or duration of exercise best achieves these benefits remains to be ascertained. METHODS/DESIGN: Forty-eight healthy young men will be recruited and randomly allocated to one of four experimental conditions for 1 week: (1) to ingest 50% more energy than normal by over-consuming their habitual diet whilst simultaneously restricting their physical activity below 4000 steps day-1 (i.e. energy surplus; SUR group); (2) the same regimen but with a daily 45-min bout of vigorous-intensity arm crank ergometry at 70% of maximum oxygen uptake (SUR + ARM group); (3) the same regimen but with a daily 45-min bout of moderate-intensity treadmill walking at 50% of maximum oxygen uptake (SUR + MOD group); (4) the same regimen but with the addition of intermittent short bouts of walking during waking hours (SUR + BREAKS group). Critically, all exercise groups will receive additional dietary energy intake to account for the energy expended by exercise, thus maintaining a matched energy surplus. At baseline and follow-up, fasted blood samples, abdominal subcutaneous adipose tissue and skeletal muscle biopsies will be obtained and oral glucose tolerance tests conducted. DISCUSSION: This study will establish the impact of different forms of daily exercise on metabolic function at the whole-body level as well as within adipose tissue and skeletal muscle in the context of a standardised energy surplus. TRIAL REGISTRATION: ISRCTN, ISRCTN18311163 . Registered on 24 June 2015.

Overnutrition, ectopic lipid and the metabolic syndrome.

The metabolic syndrome is a constellation of metabolic risk factors including atherogenic dyslipidemia (elevated serum triglycerides, reduced high-density lipoprotein (HDL) cholesterol), elevated blood pressure, dysglycemia (insulin resistance and elevated serum glucose), a pro-inflammatory state, and a prothrombotic state. Most persons with metabolic syndrome are obese, and usually have abdominal obesity. Generally, obesity is a reflection of overnutrition. A current view is that when adipose tissue fails to store all excess nutrients as triglyceride, lipid begins to accumulate in various tissues (eg, muscle, liver, pancreas, and heart). This accumulation is called ectopic lipid. Various mechanisms have been proposed whereby ectopic lipid is detrimental in different tissues; these derangements induce metabolic risk factors. The foundation of the metabolic syndrome thus appears to be overnutrition, that is, more nutrient intake than can be safely disposed by lipid oxidation. Excess dietary carbohydrate also induces ectopic lipid. Of interest, less than half of obese individuals develop metabolic syndrome. Through various mechanisms they adapt to overnutrition so as to minimize lipid overload in tissues, and consequently, prevent the syndrome.

The relationship between nutrition and prostate cancer: is more always better?

CONTEXT: Prostate cancer (PCa) remains one of the most diagnosed malignancies in the world, correlating with regions where men consume more of a so-called Western-style diet. As such, there is much interest in understanding the role of lifestyle and diet on the incidence and progression of PCa. OBJECTIVE: To provide a summary of published literature with regard to dietary macro- and micronutrients and PCa incidence and progression. EVIDENCE ACQUISITION: A literature search was completed using the PubMed database for all studies published on diet and PCa in June 2012 or earlier. Primary literature and meta-analyses were given preference over other review articles when possible. EVIDENCE SYNTHESIS: The literature was reviewed on seven dietary components: carbohydrates, protein, fat and cholesterol, vegetables, vitamins and minerals, and phytochemicals. Current literature linking these nutrients to PCa is limited at best, but trends in the published data suggest consumption of carbohydrates, saturated and ω-6 fats, and certain vitamin supplements may promote PCa risk and progression. Conversely, consumption of many plant phytochemicals and ω-3 fatty acids seem to slow the risk and progression of the disease. All other nutrients seem to have no effect or data are inconclusive. A brief summary about the clinical implications of dietary interventions with respect to PCa prevention, treatment, and survivorship is provided. CONCLUSIONS: Due to the number and heterogeneity of published studies investigating diet and PCa, it is difficult to determine what nutrients make up the perfect diet for the primary and secondary prevention of PCa. Because diets are made of multiple macro- and micronutrients, further prospective studies are warranted, particularly those investigating the relationship between whole foods instead of a single nutritional component.

The U-shaped relationship between BMI and all-cause mortality contrasts with a progressive increase in medical expenditure: a prospective cohort study.

The U-shaped relationship between body mass index (BMI) and all-cause mortality has generated uncertainty about optimal BMI. For clarification, we have related BMI to both mortality and medical expenditure. The MJ Health examination cohort of 111,949 examinees established during 1994-1996 was followed with endpoint information derived from death certificates and National Health Insurance records from 1996 to 2007. Age- and gender-specific relative risks between BMI groups were estimated by Cox and logistic regressions. The BMI and all-cause mortality relationship is U-shaped with the concave regions sitting in the region of BMI 22-26, butshifted rightward for the elderly. After excluding smokers and cancer patients at baseline, the low mortality region moved leftward to BMI 20-22. Cause-specific mortalities from respiratory disease, injury, and senility increased in the underweight group (BMI <18.5). Above 18.5, BMI was negatively associated with mortality from respiratory diseases and senility, but not with others. In contrast, irrespective of age and gender, the overall median and mean medical expenditures progressively increased with BMI, particularly beyond 22. Expenditures for injury, respiratory, circulatory diseases and senility all increased with BMI. The U-shaped BMI-mortality relation was a result of elevated death rate at both ends of the BMI scale. Increased mortality at the low end did not contribute to higher medical expenditure, maybe because the lean and frail deceased tend to die abruptly before large amount of medical expenditure was consumed. Our findings suggest that current recommendations to maintain BMI at the lower end of the desirable range remain tenable for the apparently healthy general public.

The evaluation of body composition: a useful tool for clinical practice.

Undernutrition is insufficiently detected in in- and outpatients, and this is likely to worsen during the next decades. The increased prevalence of obesity together with chronic illnesses associated with fat-free mass (FFM) loss will result in an increased prevalence of sarcopenic obesity. In patients with sarcopenic obesity, weight loss and the body mass index lack accuracy to detect FFM loss. FFM loss is related to increasing mortality, worse clinical outcomes, and impaired quality of life. In sarcopenic obesity and chronic diseases, body composition measurement with dual-energy X-ray absorptiometry, bioelectrical impedance analysis, or computerized tomography quantifies the loss of FFM. It allows tailored nutritional support and disease-specific therapy and reduces the risk of drug toxicity. Body composition evaluation should be integrated into routine clinical practice for the initial assessment and sequential follow-up of nutritional status. It could allow objective, systematic, and early screening of undernutrition and promote the rational and early initiation of optimal nutritional support, thereby contributing to reducing malnutrition-induced morbidity, mortality, worsening of the quality of life, and global health care costs.