Omega-3 to omega-6 fatty acid oxidation ratio as a novel inflammation resolution marker for metabolic complications in obesity.

BACKGROUND AND AIMS: The oxidative metabolism of polyunsaturated fatty acids (PUFAs) leads to bioactive isoprostanoids. The aim was to establish the associations of a complete urinary isoprostanoid profiling in a cohort study of carefully phenotyped obese subjects to determine possible potential differential implications for omega-6 PUFA- and omega-3 PUFA-derived isoprostanoids for obesity, metabolic indicators, and inflammation. METHODS AND RESULTS: PUFA peroxidation compounds were determined in urine samples from obese human subjects (n = 46) by liquid chromatography coupled to tandem mass spectrometry. Increased omega-6 arachidonic acid (AA) oxidation, mainly represented by 5-F2c isoprostane (5-F2c-IsoP) and metabolites of 15-F2t-IsoP, was associated with body mass index, glycated hemoglobin (HbA1c) and mean arterial blood pressure. In addition, we identified the omega-3 PUFA-derived urinary metabolites 14-F4t-NeuroP from docosahexaenoic acid (DHA) and 5-F3t-IsoP from eicosapentaenoic acid (EPA), which declined with age. The omega-3 to omega-6 oxidation ratio was a significant predictor of inflammation in obesity. CONCLUSION: The findings point to full urinary isoprostanoid profiling as a more sensitive measure of PUFA oxidative stress in obesity-induced metabolic complications compared with individual isoprostanoid measures. Furthermore, the results suggest the balance between the omega-3 and omega-6 PUFA oxidation as determinative for the consequences of oxidative stress on inflammation in obesity.

Intuitive eating is associated with weight loss after bariatric surgery in women.

BACKGROUND: Although the data on eating behavior after bariatric surgery are substantial, data on "intuitive eating" are lacking. OBJECTIVE: The aim of this study was to evaluate the link between intuitive eating and weight loss after bariatric surgery. METHODS: This cross-sectional study used a self-administered questionnaire freely available on social networks and targeted women who had undergone bariatric surgery. Intuitive eating was evaluated with the Intuitive Eating Scale-2 (IES-2). The 3 questionnaire subscores (Eating for Physical Rather than Emotional Reasons, Reliance on Hunger and Satiety Cues, and Unconditional Permission to Eat) were also analyzed. The relation between IES-2 scores and the relative variation in body mass index [BMI (in kg/m2)] was assessed with linear regression models. Adjusted ß (ßAdj) and standardized ß $( {{\rm{\beta }}_{{\rm{Adj}}}^{{\rm{STD}}}} )$ were reported. RESULTS: We analyzed the responses of 401 women with a mean age of 39 ± 11 y, a mean preoperative BMI of 45.5 ± 7.9, and a mean current BMI of 30.5 ± 7. The mean relative BMI loss was 32.7 ± 12.9%, and the mean IES-2 score was 3.3 ± 0.6. The total IES-2 score was associated with the relative BMI loss, with ∼2.6% BMI loss for each 1-point increase in the IES-2 score [PAdj = 0.007; ßAdj = -2.57 (95% CI: -4.44, -0.70); ${\rm{\beta }}_{{\rm{Adj}}}^{{\rm{STD}}}$= -0.12] after adjusting for elapsed time since surgery and type of surgery. Eating for Physical Rather than Emotional Reasons was the subscore most strongly associated with BMI change after adjustment [PAdj = 0.002; ßAdj = -2.08 (95% CI: -3.37, 0.79); ${\rm{\beta }}_{{\rm{Adj}}}^{{\rm{STD}}}$ = -0.14]. CONCLUSIONS: This study highlights a significant association between intuitive eating and BMI decrease after bariatric surgery. Furthermore, eating behaviors changed with increasing time since surgery. An intuitive nutritional approach may be complementary with bariatric surgery in the postoperative phase, which should prompt complementary prospective studies to evaluate the effectiveness of therapeutic education programs centered on intuitive eating in the postoperative period.

Combination of nutritional polyphenols supplementation with exercise training counteracts insulin resistance and improves endurance in high-fat diet-induced obese rats.

Separately, polyphenols and exercise are known to prevent insulin resistance (IR) but their combined curative effects on established obesity and IR require further investigation. Therefore, we compared the metabolic effects of a combination of exercise and grape polyphenols supplementation in obese IR rats with high-fat diet (EXOPP) to the effect of high-fat diet alone (HF) or with a nutritional supplementation of grape polyphenols (PP) or with endurance exercise (EXO) during 8 wks. We observed an improvement of systemic and skeletal muscle insulin sensitivity in EXO and EXOPP rats. EXOPP rats compared to HF rats presented a lower insulinemia and HOMA-IR with higher liver and muscle glycogen contents. Interestingly, EXOPP rats had a 68% enhanced endurance capacity compared to EXO rats with also a higher activation of AMPK compared to sedentary and EXO rats with increased lipid oxidation. Together, our results suggest that grape polyphenols supplementation combined with exercise has a synergistic effect by increasing muscle lipid oxidation and sparing glycogen utilization which thus enhances endurance capacity. Our data highlight that in cases of established obesity and IR, the combination of nutritional grape polyphenols supplementation and exercise heighten and intensify their individual metabolic effects.

Grape polyphenols supplementation reduces muscle atrophy in a mouse model of chronic inflammation.

OBJECTIVES: Polyphenols (PP) have demonstrated beneficial effects on low-grade inflammation and oxidative stress; however, little is known about their effect on highly inflamed muscle. The purposes of this study were (i) to evaluate muscle alteration induced by high-grade inflammation, and (ii) to test the effects of red grape PP supplementation on these alterations. METHODS: We used a transgenic mice model (transforming growth factor [TGF] mice) to develop a high T cell-dependent inflammation and C57 BL/6 control (CTL) mice model. Skeletal muscles of TGF and CTL mice were investigated for inflammation, atrophy and oxidative stress markers. Isolated mitochondria from hindlimb muscles were used for respiration with pyruvate as substrate and oxidative damages were measured by Western blot. TGF mice were supplemented with a mixture of red grape polyphenols (50 mg/kg/d) for 4 wk. Data were analyzed by one-way analysis of variance (ANOVA) and post hoc Bonferroni's multiple comparison tests. RESULTS: TGF mice presented skeletal muscle inflammation, oxidative stress, mitochondrial alteration and muscle atrophy. Atrophy was associated with two distinct pathways: (i) one linked to inflammation, NF-κB activation and increased ubiquitin ligase expression, and (ii) one dependent on reactive oxygen species (ROS) production leading to damaged mitochondria accumulation and activation of caspase-9 and 3. Supplementation of TGF mice with a mixture of red grape polyphenols (50 mg/kg/d) for 4 wk improved mitochondrial function and highly decreased caspases activation, which allowed muscle atrophy mitigation. CONCLUSIONS: These observations suggest that nutritional dosages of red grape polyphenols might be beneficial for reducing skeletal muscle atrophy, even in a high-grade inflammation environment.

Systems medicine approaches for the definition of complex phenotypes in chronic diseases and ageing. From concept to implementation and policies.

Chronic diseases are diseases of long duration and slow progression. Major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases, diabetes, rheumatologic diseases and mental health) represent the predominant health problem of the Century. The prevention and control of NCDs are the priority of the World Health Organization 2008 Action Plan, the United Nations 2010 Resolution and the European Union 2010 Council. The novel trend for the management of NCDs is evolving towards integrative, holistic approaches. NCDs are intertwined with ageing. The European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) has prioritised NCDs. To tackle them in their totality in order to reduce their burden and societal impact, it is proposed that NCDs should be considered as a single expression of disease with different risk factors and entities. An innovative integrated health system built around systems medicine and strategic partnerships is proposed to combat NCDs. It includes (i) understanding the social, economic, environmental, genetic determinants, as well as the molecular and cellular mechanisms underlying NCDs; (ii) primary care and practice-based interprofessional collaboration; (iii) carefully phenotyped patients; (iv) development of unbiased and accurate biomarkers for comorbidities, severity and follow up of patients; (v) socio-economic science; (vi) development of guidelines; (vii) training; and (viii) policy decisions. The results could be applicable to all countries and adapted to local needs, economy and health systems. This paper reviews the complexity of NCDs intertwined with ageing. It gives an overview of the problem and proposes two practical examples of systems medicine (MeDALL) applied to allergy and to NCD co-morbidities (MACVIA-LR, Reference Site of the European Innovation Partnership on Active and Healthy Ageing).

Dietary antioxidants: Do they have a role to play in the ongoing fight against abnormal glucose metabolism?

Overfeeding, an increased intake of saturated fatty acids, and sugary foods are key dietary changes that have occurred in recent decades in addition to the emergence of the obesity epidemic. In addition to an increase in energy storage as fat, these dietary changes are accompanied by an increase in mitochondrial macronutrient oxidation, leading to an excessive free radical production and, hence, oxidative stress. The latter has long been considered a central mechanism linking nutrient overload, insulin resistance, the metabolic syndrome, and diabetes. However, food, through fruit and vegetable consumption, also can be a great source of antioxidants that protect the body against oxidative damage and insulin resistance and thus help cope with the metabolic backlash of the energy-dense Westernized diet. Experimental data are in favor of the beneficial role conveyed by antioxidants in glucose metabolism, but clinical data in humans remain controversial. This review therefore aimed to sort out any underlying discrepancies and provide an overall clear view of the role of antioxidants in the ongoing fight against abnormal glucose metabolism.

Systems medicine and integrated care to combat chronic noncommunicable diseases.

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

Antioxidants and glucose metabolism disorders.

PURPOSE OF REVIEW: Recent evidence suggests that oxidative stress is a cornerstone of the metabolic mechanisms by which overfeeding leads to insulin resistance. This review is an update of the most recent arguments in favor of this theory and of the possible role of antioxidants. RECENT FINDINGS: Reactive oxidative species (ROS) are produced by multiple pathways within the cell and are essential for many cellular functions. ROS production is balanced by enzymatic and nonenzymatic antioxidant systems. The perturbation of the pro-oxidant/antioxidant balance can lead to increased oxidative damage of macromolecules, a phenomenon known as 'oxidative stress'. ROS are involved both in insulin signal transduction and in insulin resistance when produced in excess. Overfeeding, saturated fatty acids, and obesity play a key role in the excessive production of ROS. However, a diet rich in fruits and vegetables, and therefore antioxidants, has demonstrated beneficial effects against oxidative damages and insulin resistance. SUMMARY: Experimental data are in favor of a beneficial role of antioxidants in glucose metabolism, but clinical data in humans are more controversial. Even if a diet rich in fruits and vegetables could provide an optimal mix of antioxidants, it remains unclear whether supplementation with antioxidants alone can reproduce the same effect.