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 (p = 0.029) and fibrosis severity (p = 0.010). There was a trend to an association between IMCL and decreased Akt phosphorylation (p = 0.059), despite no association with insulin resistance. In turn, hepatic steatosis (p = 0.015) and inflammation (p = 0.013) were associated with decreased Akt phosphoryation. Citrate synthase activity was lower in obese patients (p = 0.047) whereas complex I (p = 0.040) and III (p = 0.036) activities were higher, compared with controls. Finally, in obese patients, complex I activity increased with progressive steatosis (p = 0.049) and with a trend with fibrosis severity (p = 0.056). 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

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 = 3776, 74.6%), by internal medicine specialists 14.2% (n = 718) and by primary care/general practice physicians 8.2% (n = 417). 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 20 mg (76.5%) and 15 mg (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

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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

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Takotsubo syndrome during induction of general anaesthesia

International audienceA 77-year-old female was admitted in our hospital for uterine prolapse surgery. She developed ventricular tachycardia during induction of general anaesthesia and after initial symptomatic measures, she was transferred to the coronary care unit. Heart failure persisted and electro-cardiographic changes mimicking acute myocardial infarction appeared. Coronary angiography was normal and left ventriculography revealed akinesis of the apical region of the left ventricle and apical ballooning during systole, with relative sparing of the base of the heart. Complete recovery of left ventricular function occurred 8 days after the initial onset of symptoms. A diagnosis of Takotsubo syndrome was made on the basis of consistent clinical and laboratory findings, typical echocardio-graphy and angiography findings, and reversible course. This case emphasises the importance of being aware of uncommon causes of cardiac dysfunction in stressful situations, especially during induction of general anaesthesia. Takotsubo cardiomyopathy, or transient left ventricular apical ballooning syndrome, was first described in Japan as acute systolic heart failure caused by transient left ventricle apical akinesis [1]. This syndrome is usually triggered by stressful situations, and mainly affects elderly female patients [2]. The peri-operative period is well-known to induce stress in patients, and this diagnosis should be considered when a patient presents with left ventricular dysfunction or electrocardiographic changes mimicking acute myocardial infarction in stressful situations [3, 4], especially during the induction of general anaesthesia. We report the case of a 77-year-old female with Takotsubo syndrome that revealed itself during the induction of general anaesthesia. Case report A 77-year-old female was admitted to our hospital for vaginal repair of uterine prolapse. She had a history of facial neuralgia treated by clonazepam, venous insuffi-ciency, previous laparotomy under general anaesthesia and bilateral cataract surgery under peribulbar anaesthesia. There were no anaesthetic complications during these procedures. Pre-operative evaluation including electro-cardiography was unremarkable, arterial pressure was 150 ⁄ 80 mmHg, and cardiopulmonary auscultation was normal. The patient decided against spinal anaesthesia, and it was therefore decided to administer a target-controlled infusion (TCI) of propofol, combined with regional anaesthesia (bilateral paracervical and pudendal nerve blocks). Before transfer to the operating room, the patient received 50 mg hydroxyzine. In addition to standard monitoring, anaesthesia depth monitoring was performed during surgery to measure bispectral index (BIS). Her arterial pressure was 195 ⁄ 92 mmHg, and heart rate was 70 beats.min)1. Oxygen saturation was 95% with the patient breathing air. Pre-oxygenation was administered until the expired oxygen reached a fraction of 0.9

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

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Overfeeding increases postprandial endotoxemia in men: Inflammatory outcome may depend on LPS transporters LBP and sCD14

International audienceSCOPE: Low-grade inflammation is a recognized hallmark of obesity. Endotoxins absorbed after high-fat meals have recently been implicated. Plasma lipopolysaccharides binding protein (LBP) and soluble cluster of differentiation 14 (sCD14) have also been suggested as clinical markers of endotoxemia. In mice, the ratio LBP/sCD14 has been associated with high fat diet induced inflammation. We tested the hypothesis that healthy subjects develop inflammation differently during weight gain according to changes of LBP/sCD14 ratio. METHODS AND RESULTS: Eighteen healthy men were overfed during 8 wk (+760 kcal/day). Endotoxemia, sCD14, LBP, and IL-6 were measured before and after overfeeding (OF) at fasting (n = 18) and postprandially (subcohort, n = 8). OF did not modify fasting IL-6 but increased the LBP/sCD14 ratio (P = 0.017). Subjects were categorized into tertiles for LBP/sCD14 ratio variation. Subjects in the highest tertile (+90% LBP/sCD14) increased plasma IL-6 (+26%) versus the lowest tertile due to a decrease of sCD14 associated with high LBP. The postprandial accumulation of endotoxins increased after OF (+160%). However, only four responding subjects presented increased postprandial IL-6 accumulation. CONCLUSION: OF increases postprandial endotoxemia but the inflammatory outcome may be modulated by endotoxin handling in plasma. This study supports a new concept whereby inflammation setup during the initial phase of weight gain is linked to the relative variations of LBP and sCD14

Subcutaneous Adipose Tissue Remodeling during the Initial Phase of Weight Gain Induced by Overfeeding in Humans

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