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      Premorbid obesity, but not nutrition, prevents critical illness‐induced muscle wasting and weakness

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          Abstract

          Background

          The ‘obesity paradox’ of critical illness refers to better survival with a higher body mass index. We hypothesized that fat mobilized from excess adipose tissue during critical illness provides energy more efficiently than exogenous macronutrients and could prevent lean tissue wasting.

          Methods

          In lean and premorbidly obese mice, the effect of 5 days of sepsis‐induced critical illness on body weight and composition, muscle wasting, and weakness was assessed, each with fasting and parenteral feeding. Also, in lean and overweight/obese prolonged critically ill patients, markers of muscle wasting and weakness were compared.

          Results

          In mice, sepsis reduced body weight similarly in the lean and obese, but in the obese with more fat loss and less loss of muscle mass, better preservation of myofibre size and muscle force, and less loss of ectopic lipids, irrespective of administered feeding. These differences between lean and obese septic mice coincided with signs of more effective hepatic fatty acid and glycerol metabolism, and ketogenesis in the obese. Also in humans, better preservation of myofibre size and muscle strength was observed in overweight/obese compared with lean prolonged critically ill patients.

          Conclusions

          During critical illness premorbid obesity, but not nutrition, optimized utilization of stored lipids and attenuated muscle wasting and weakness.

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          Most cited references29

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          Molecular mediators of hepatic steatosis and liver injury.

          Obesity and its associated comorbidities are among the most prevalent and challenging conditions confronting the medical profession in the 21st century. A major metabolic consequence of obesity is insulin resistance, which is strongly associated with the deposition of triglycerides in the liver. Hepatic steatosis can either be a benign, noninflammatory condition that appears to have no adverse sequelae or can be associated with steatohepatitis: a condition that can result in end-stage liver disease, accounting for up to 14% of liver transplants in the US. Here we highlight recent advances in our understanding of the molecular events contributing to hepatic steatosis and nonalcoholic steatohepatitis.
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            Differential effects of fat and sucrose on the development of obesity and diabetes in C57BL/6J and A/J mice.

            We have previously demonstrated that the C57BL/6J (B/6J) mouse will develop severe obesity, hyperglycemia, and hyperinsulinemia if weaned onto a high-fat, high-sucrose (HH) diet. In the present study, we compared the effects of fat and sucrose separately and in combination on diabetes- and obesity-prone B/6J and diabetes- and obesity-resistant A/J mice. After 4 months, the feed efficiency ([FE] weight gained divided by calories consumed) did not differ across diets in A/J mice, but B/6J mice showed a significantly increased FE for fat. That is, B/6J mice gained more weight on high-fat diets without consuming more calories than A/J mice. The increase in FE was related to adipocyte hyperplasia in B/6J mice on high-fat diets. Fat-induced obesity in B/6J mice was unrelated to adrenal cortical activity. In the absence of fat, sucrose produced a decreased in FE in both strains. Animals fed a low-fat, high-sucrose (LH) diet were actually leaner than animals fed a high-complex-carbohydrate diet. Fat was also found to be the critical stimulus for hyperglycemia and hyperinsulinemia in B/6J mice. In the absence of fat, sucrose had no effect on plasma glucose or insulin. These data clearly show that across these two strains of mice, genetic differences in the metabolic response to fat are more important in the development of obesity and diabetes than the increased caloric content of a high-fat diet.
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              Neuromuscular dysfunction acquired in critical illness: a systematic review.

              To determine the prevalence, risk factors, and outcomes of critical illness neuromuscular abnormalities (CINMA). Systematic review. MEDLINE, EMBASE, CINAHL, and the Cochrane Library were searched for reports on adult ICU patients who were evaluated for CINMA clinically and electrophysiologically. Studies were included if they contained sufficient data to quantify the association between CINMA and relevant exposures and/or outcome variables. CINMA was diagnosed in 655 of 1421 [46% (95% confidence interval 43-49%)] adult ICU patients enrolled in 24 studies, all with inclusion criteria of sepsis, multi-organ failure, or prolonged mechanical ventilation. Diagnostic criteria for CINMA were not uniform, and few reports unequivocally differentiated between polyneuropathy, myopathy, and mixed types of CINMA. The risk of CINMA was associated with hyperglycemia (and inversely associated with tight glycemic control), the systemic inflammatory response syndrome, sepsis, multiple organ dysfunction, renal replacement therapy, and catecholamine administration. Across studies, there was no consistent relationship between CINMA and patient age, gender, severity of illness, or use of glucocorticoids, neuromuscular blockers, aminoglycosides, or midazolam. Unadjusted mortality was not increased in the majority of patients with CINMA, but mechanical ventilation and ICU and hospital stay were prolonged. The risk of CINMA is nearly 50% in ICU patients with sepsis, multi-organ failure, or protracted mechanical ventilation. The association of CINMA with frequently cited CINMA risk factors (glucocorticoids, neuromuscular blockers) and with short-term survival is uncertain. Available data indicate glycemic control as a potential strategy to decrease CINMA risk.
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                Author and article information

                Contributors
                lies.langouche@kuleuven.be
                Journal
                J Cachexia Sarcopenia Muscle
                J Cachexia Sarcopenia Muscle
                10.1007/13539.2190-6009
                JCSM
                Journal of Cachexia, Sarcopenia and Muscle
                John Wiley and Sons Inc. (Hoboken )
                2190-5991
                2190-6009
                20 July 2016
                February 2017
                : 8
                : 1 ( doiID: 10.1002/jcsm.v8.1 )
                : 89-101
                Affiliations
                [ 1 ] Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine KU Leuven 3000 LeuvenBelgium
                [ 2 ] Exercise Physiology Research Group, Department of KinesiologyKU Leuven 3000 LeuvenBelgium
                Author notes
                [*] [* ] Correspondence to: Lies Langouche, Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49 bus 503, B‐3000 Leuven, Belgium. Phone: +32 16 330524, Email: lies.langouche@ 123456kuleuven.be
                Article
                JCSM12131 JCSM-D-15-00197
                10.1002/jcsm.12131
                5326828
                27897405
                35d5ccf0-3ea6-4811-8375-3199f383e0ce
                © 2016 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 16 November 2015
                : 11 May 2016
                : 20 May 2016
                Page count
                Figures: 8, Tables: 0, Pages: 13, Words: 5932
                Funding
                Funded by: Flemish Government
                Award ID: METH08/07
                Funded by: European Research Council Advanced Grant
                Award ID: AdvG‐2012‐321670
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                jcsm12131
                jcsm12131-hdr-0001
                February 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.0.7 mode:remove_FC converted:27.02.2017

                Orthopedics
                critical illness,obesity,skeletal muscle,metabolism
                Orthopedics
                critical illness, obesity, skeletal muscle, metabolism

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