25 research outputs found
Differential effects of saturated versus unsaturated dietary fatty acids on weight gain and myocellular lipid profiles in mice
OBJECTIVE: In conditions of continuous high-fat (HF) intake, the degree of saturation of the fatty acids (FAs) in the diet might have a crucial role in the onset of obesity and its metabolic complications. In particular, the FA composition of the diet might influence the storage form of lipids inside skeletal muscle. The aim of the present study was to examine whether the FA composition of HF diets differentially affects weight gain and accumulation of myocellular triacylglycerol (TAG) and diacylglycerol (DAG). Furthermore, we examined whether the FA composition of the diet was reflected in the composition of the myocellular lipid intermediates.DESIGN: C57Bl6 mice were fed HF diets (45% energy) mainly containing palm oil (PO), cocoa butter (CB), olive oil (OO) or safflower oil (SO; n=6 per group) for 8 weeks. A low-fat diet (10% energy, PO) was used as control. Body weight was monitored weekly. At the end of the dietary intervention, myocellular TAG and DAG content and profiles were measured.RESULTS: We here show that HF_CB prevented weight gain after 8 weeks of HF feeding. Furthermore, the HF diet rich in SO prevented the accumulation of both myocellular TAG and DAG. Interestingly, the FA composition of DAG and TAG in skeletal muscle was a reflection of the dietary FA composition.CONCLUSION: Already after a relatively short period, the dietary FA intake relates to the FA composition of the lipid metabolites in the muscle. A diet rich in polyunsaturated FAs seems to prevent myocellular lipid accumulation.<br/
Muscle-Specific Adaptations, Impaired Oxidative Capacity and Maintenance of Contractile Function Characterize Diet-Induced Obese Mouse Skeletal Muscle
BACKGROUND:The effects of diet-induced obesity on skeletal muscle function are largely unknown, particularly as it relates to changes in oxidative metabolism and morphology. PRINCIPAL FINDINGS:Compared to control fed mice, mice fed a high fat diet (HFD; 60% kcal: fat) for 8 weeks displayed increased body mass and insulin resistance without overt fasting hyperglycemia (i.e. pre-diabetic). Histological analysis revealed a greater oxidative potential in the HFD gastrocnemius/plantaris (increased IIA, reduced IIB fiber-type percentages) and soleus (increased I, IIA cross-sectional areas) muscles, but no change in fiber type percentages in tibialis anterior muscles compared to controls. Intramyocellular lipid levels were significantly increased relative to control in HFD gastrocnemius/plantaris, but were similar to control values in the HFD soleus. Using a novel, single muscle fiber approach, impairments in complete palmitate and glucose oxidation (72.8+/-6.6% and 61.8+/-9.1% of control, respectively; p<0.05) with HFD were detected. These reductions were consistent with measures made using intact extensor digitorum longus and soleus muscles. Compared to controls, no difference in succinate dehydrogenase or citrate synthase enzyme activities were observed between groups in any muscle studied, however, short-chain fatty acyl CoA dehydrogenase (SCHAD) activity was elevated in the HFD soleus, but not tibialis anterior muscles. Despite these morphological and metabolic alterations, no significant difference in peak tetanic force or low-frequency fatigue rates were observed between groups. CONCLUSIONS:These findings indicate that HFD induces early adaptive responses that occur in a muscle-specific pattern, but are insufficient to prevent impairments in oxidative metabolism with continued high-fat feeding. Moreover, the morphological and metabolic changes which occur with 8 weeks of HFD do not significantly impact muscle contractile properties
Liver and Muscle in Morbid Obesity: The Interplay of Fatty Liver and Insulin Resistance
INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) can be seen as a manifestation of overnutrition. The muscle is a central player in the adaptation to energy overload, and there is an association between fatty-muscle and -liver. We aimed to correlate muscle morphology, mitochondrial function and insulin signaling with NAFLD severity in morbid obese patients. METHODS: Liver and deltoid muscle biopsies were collected during bariatric surgery in NAFLD patients. NAFLD Activity Score and Younossi's classification for nonalcoholic steatohepatitis (NASH) were applied to liver histology. Muscle evaluation included morphology studies, respiratory chain complex I to IV enzyme assays, and analysis of the insulin signaling cascade. A healthy lean control group was included for muscle morphology and mitochondrial function analyses. RESULTS: Fifty one NAFLD patients were included of whom 43% had NASH. Intramyocellular lipids (IMCL) were associated with the presence of NASH (OR 12.5, p<0.001), progressive hepatic inflammation (pâ=â0.029) and fibrosis severity (pâ=â0.010). There was a trend to an association between IMCL and decreased Akt phosphorylation (pâ=â0.059), despite no association with insulin resistance. In turn, hepatic steatosis (pâ=â0.015) and inflammation (pâ=â0.013) were associated with decreased Akt phosphoryation. Citrate synthase activity was lower in obese patients (pâ=â0.047) whereas complex I (pâ=â0.040) and III (pâ=â0.036) activities were higher, compared with controls. Finally, in obese patients, complex I activity increased with progressive steatosis (pâ=â0.049) and with a trend with fibrosis severity (pâ=â0.056). CONCLUSIONS: In morbid obese patients, presence of IMCL associates with NASH and advanced fibrosis. Muscle mitochondrial dysfunction does not appear to be a major driving force contributing to muscle fat accumulation, insulin resistance or liver disease. Importantly, insulin resistance in muscle might occur at a late point in the insulin signaling cascade and be associated with IMCL and NAFLD severity
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Obesity, diabetes and longevity in the Gulf: is there a Gulf Metabolic Syndrome?
The Gulf is experiencing a pandemic of lifestyle-induced obesity and type 2 diabetes mellitus (T2DM), with rates exceeding 50 and 30%, respectively. It is likely that T2DM represents the tip of a very large metabolic syndrome iceberg, which precedes T2DM by many years and is associated with abnormal/ectopic fat distribution, pathological systemic oxidative stress and inflammation. However, the definitions are still evolving with the role of different fat depots being critical. Hormetic stimuli, which include exercise, calorie restriction, temperature extremes, dehydration and even some dietary components (such as plant polyphenols), may well modulate fat deposition. All induce physiological levels of oxidative stress, which results in mitochondrial biogenesis and increased anti-oxidant capacity, improving metabolic flexibility and the ability to deal with lipids. We propose that the Gulf Metabolic Syndrome results from an unusually rapid loss of hormetic stimuli within an epigenetically important time frame of 2-3 generations. Epigenetics indicates that thriftiness can be programmed by the environment and passed down through several generations. Thus this loss of hormesis can result in continuation of metabolic inflexibility, with mothers exposing the foetus to a milieu that perpetuates a stressed epigenotype. As the metabolic syndrome increases oxidative stress and reduces life expectancy, a better descriptor may therefore be the Lifestyle-Induced Metabolic Inflexibility and accelerated AGEing syndrome â LIMIT-AGE. As life expectancy in the Gulf begins to fall, with perhaps a third of this life being unhealthy â including premature loss of sexual function, it is vital to detect evidence of this condition as early in life as possible. One effective way to do this is by detecting evidence of metabolic inflexibility by studying body fat content and distribution by magnetic resonance (MR). The Gulf Metabolic Syndrome thus represents an accelerated form of the metabolic syndrome induced by the unprecedented rapidity of lifestyle change in the region, the stress of which is being passed from generation to generation and may be accumulative. The fundamental cause is probably due to a rapid increase in countrywide wealth. This has benefited most socioeconomic groups, resulting in the development of an obesogenic environment as the result of the rapid adoption of Western labour saving and stress relieving devices (e.g. cars and air conditioning), as well as the associated high calorie diet
International longitudinal registry of patients with atrial fibrillation and treated with rivaroxaban: RIVaroxaban Evaluation in Real life setting (RIVER)
Background
Real-world data on non-vitamin K oral anticoagulants (NOACs) are essential in determining whether evidence from randomised controlled clinical trials translate into meaningful clinical benefits for patients in everyday practice. RIVER (RIVaroxaban Evaluation in Real life setting) is an ongoing international, prospective registry of patients with newly diagnosed non-valvular atrial fibrillation (NVAF) and at least one investigator-determined risk factor for stroke who received rivaroxaban as an initial treatment for the prevention of thromboembolic stroke. The aim of this paper is to describe the design of the RIVER registry and baseline characteristics of patients with newly diagnosed NVAF who received rivaroxaban as an initial treatment.
Methods and results
Between January 2014 and June 2017, RIVER investigators recruited 5072 patients at 309 centres in 17 countries. The aim was to enroll consecutive patients at sites where rivaroxaban was already routinely prescribed for stroke prevention. Each patient is being followed up prospectively for a minimum of 2-years. The registry will capture data on the rate and nature of all thromboembolic events (stroke / systemic embolism), bleeding complications, all-cause mortality and other major cardiovascular events as they occur. Data quality is assured through a combination of remote electronic monitoring and onsite monitoring (including source data verification in 10% of cases). Patients were mostly enrolled by cardiologists (n =â3776, 74.6%), by internal medicine specialists 14.2% (n =â718) and by primary care/general practice physicians 8.2% (n =â417). The mean (SD) age of the population was 69.5 (11.0) years, 44.3% were women. Mean (SD) CHADS2 score was 1.9 (1.2) and CHA2DS2-VASc scores was 3.2 (1.6). Almost all patients (98.5%) were prescribed with once daily dose of rivaroxaban, most commonly 20âmg (76.5%) and 15âmg (20.0%) as their initial treatment; 17.9% of patients received concomitant antiplatelet therapy. Most patients enrolled in RIVER met the recommended threshold for AC therapy (86.6% for 2012 ESC Guidelines, and 79.8% of patients according to 2016 ESC Guidelines).
Conclusions
The RIVER prospective registry will expand our knowledge of how rivaroxaban is prescribed in everyday practice and whether evidence from clinical trials can be translated to the broader cross-section of patients in the real world
When COVID-19 delays the management of an urgent heart condition: A rare case of a spontaneous dissection of two coronary arteries
International audienc
Paroxysmal atrial fibrillation associated with a moderate form of COVIDâ19 in a middleâaged man with low cardiovascular risk factor: More still needs to be done in this topic
International audienc
Paroxysmal atrial fibrillation associated with a moderate form of COVID-19 in a middle-aged man with low cardiovascular risk factor: More still needs to be done in this topic
International audienc
A reproducible, self-reported, field-based tool for monitoring ovarian hormone status and body weight variations in female athletes: the Answ'Her questionnaire
BACKGROUND: Intra-individual factors like ovarian hormone profiles and body weight variations may influence sports practice and performance in female athletes and need to be characterized. The "Answ'Her"questionnaire was designed to develop a relevant and reproducible fieldbased tool to assess self-reported ovarian hormone status (natural menstrual cycle and hormonal contraceptive use) and body weight variations practices among female athletes. METHODS: French females with a regular sports practice responded (once: N.=210; twice: N.=86; thrice: N.=66) to this 73-item questionnaire reporting their ovarian hormone status, associated symptoms, perceived influence on sports practice, and body weight variations. Reproducibility was evaluated, then a descriptive cross-sectional analysis was conducted on athletes. RESULTS: Reproducibility was verified with 92% of Lin's correlation concordance coefficients above 0.7 and 100% of weighted agreements above 70%. Ultimately 185 female athletes (23.0±4.8 years) were included in the cross-sectional analysis. Whether they used hormonal contraceptive (46.5%) or not (53.5%), most of the athletes perceived a negative impact of their ovarian hormone status on sports practice (78.7%) and performance (84.7%). Overall, 77.3% of the athletes had experienced body weight variations that were significantly associated with an interruption of menses (>3 months) and menses irregularity over the last three years. CONCLUSIONS: The Answ'Her questionnaire is a simple and effective reproducible field-based tool for the self-reported characterisation of female athlete ovarian hormone status and body weight variations. It could be used for a unique and simple overview of the athlete situation but also in a longitudinal design to assess the athlete's evolution and/or effectiveness of implanted training strategies
Subcutaneous Adipose Tissue Remodeling during the Initial Phase of Weight Gain Induced by Overfeeding in Humans
International audienc