Obesity attenuates inflammation, protein catabolism, dyslipidaemia, and muscle weakness during sepsis, independent of leptin

Muscle weakness is a frequently occurring complication of sepsis, associated with increased morbidity and mortality. Interestingly, obesity attenuates sepsis‐induced muscle wasting and weakness. As the adipokine leptin is strongly elevated in obesity and has been shown to affect muscle homeostasis in non‐septic conditions, we aimed to investigate whether leptin mediates the protective effect of obesity on sepsis‐induced muscle weakness.

[1]  G. Van den Berghe,et al.  Altered cholesterol homeostasis in critical illness-induced muscle weakness: effect of exogenous 3-hydroxybutyrate , 2021, Critical Care.

[2]  J. Schefold,et al.  Muscular weakness and muscle wasting in the critically ill , 2020, Journal of cachexia, sarcopenia and muscle.

[3]  Y. Mineur,et al.  Origin and Function of Stress-Induced IL-6 in Murine Models , 2020, Cell.

[4]  F. Reis,et al.  Diet‐induced rodent models of obesity‐related metabolic disorders—A guide to a translational perspective , 2020, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[5]  Y. Mineur,et al.  Origin and Function of Stress-Induced IL-6 in Murine Models , 2020, Cell.

[6]  O. Meilhac,et al.  High-density lipoproteins during sepsis: from bench to bedside , 2020, Critical Care.

[7]  J. Holst,et al.  Glucagon Resistance at the Level of Amino Acid Turnover in Obese Subjects With Hepatic Steatosis , 2020, Diabetes.

[8]  Stephan von Haehling,et al.  Ethical guidelines for publishing in the Journal of Cachexia, Sarcopenia and Muscle: update 2015 , 2015, Journal of cachexia, sarcopenia and muscle.

[9]  R. Pearse,et al.  Elevated urea-to-creatinine ratio provides a biochemical signature of muscle catabolism and persistent critical illness after major trauma , 2019, Intensive Care Medicine.

[10]  G. Van den Berghe,et al.  Adipose tissue protects against sepsis-induced muscle weakness in mice: from lipolysis to ketones , 2019, Critical Care.

[11]  Alicia Mayeuf-Louchart,et al.  MuscleJ: a high-content analysis method to study skeletal muscle with a new Fiji tool , 2018, Skeletal Muscle.

[12]  M. Singer,et al.  Metabolic phenotype of skeletal muscle in early critical illness , 2018, Thorax.

[13]  G. Frühbeck,et al.  The increase in fiber size in male rat gastrocnemius after chronic central leptin infusion is related to activation of insulin signaling , 2017, Molecular and Cellular Endocrinology.

[14]  J. Holst,et al.  Role of Glucagon in Catabolism and Muscle Wasting of Critical Illness and Modulation by Nutrition , 2017, American journal of respiratory and critical care medicine.

[15]  S. Hussain,et al.  Differential Regulation of the Autophagy and Proteasome Pathways in Skeletal Muscles in Sepsis , 2017, Critical care medicine.

[16]  M. van Griensven,et al.  Leptin Protects Against Mortality and Organ Dysfunction in A Two-Hit Trauma/Sepsis Model and is IL-6-Dependent , 2017, Shock.

[17]  H. S. Hundal,et al.  Lipid modulation of skeletal muscle mass and function , 2016, Journal of cachexia, sarcopenia and muscle.

[18]  G. Van den Berghe,et al.  Premorbid obesity, but not nutrition, prevents critical illness‐induced muscle wasting and weakness , 2016, Journal of cachexia, sarcopenia and muscle.

[19]  J. Vincent,et al.  Being Overweight Is Associated With Greater Survival in ICU Patients: Results From the Intensive Care Over Nations Audit* , 2015, Critical care medicine.

[20]  S. Koo,et al.  Systemic autophagy insufficiency compromises adaptation to metabolic stress and facilitates progression from obesity to diabetes , 2014, Nature Communications.

[21]  G. Frühbeck,et al.  Leptin administration activates irisin-induced myogenesis via nitric oxide-dependent mechanisms, but reduces its effect on subcutaneous fat browning in mice , 2014, International Journal of Obesity.

[22]  Rahul Phadke,et al.  Acute skeletal muscle wasting in critical illness. , 2013, JAMA.

[23]  Niels Peek,et al.  Body Mass Index Is Associated With Hospital Mortality in Critically Ill Patients: An Observational Cohort Study , 2013, Critical care medicine.

[24]  K. Walley,et al.  One size does not fit all in severe infection: obesity alters outcome, susceptibility, treatment, and inflammatory response , 2013, Critical Care.

[25]  G. Van den Berghe,et al.  Impact of early parenteral nutrition on metabolism and kidney injury. , 2013, Journal of the American Society of Nephrology : JASN.

[26]  G. Van den Berghe,et al.  Impact of early nutrient restriction during critical illness on the nonthyroidal illness syndrome and its relation with outcome: a randomized, controlled clinical study. , 2013, The Journal of clinical endocrinology and metabolism.

[27]  T. Hornberger,et al.  Muscle Fiber Type-Dependent Differences in the Regulation of Protein Synthesis , 2012, PloS one.

[28]  C. Spies,et al.  Early type II fiber atrophy in intensive care unit patients with nonexcitable muscle membrane , 2012, Critical care medicine.

[29]  G. Van den Berghe,et al.  Early versus Late Parenteral Nutrition in Critically Ill Adults , 2011, The New England journal of medicine.

[30]  Jan Gunst,et al.  Insufficient activation of autophagy allows cellular damage to accumulate in critically ill patients. , 2011, The Journal of clinical endocrinology and metabolism.

[31]  Alexander Doyle,et al.  Toll‐like receptor 4 mediates lipopolysaccharide‐induced muscle catabolism via coordinate activation of ubiquitin‐proteasome and autophagy‐lysosome pathways , 2011, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[32]  P. Parsons,et al.  The association between BMI and plasma cytokine levels in patients with acute lung injury. , 2010, Chest.

[33]  M. van Meurs,et al.  Leptin Exacerbates Sepsis-Mediated Morbidity and Mortality , 2010, The Journal of Immunology.

[34]  K. Craig,et al.  Coding of facial expressions of pain in the laboratory mouse , 2010, Nature Methods.

[35]  S. O’Rahilly,et al.  CNS Leptin Action Modulates Immune Response and Survival in Sepsis , 2010, The Journal of Neuroscience.

[36]  D. Metzger,et al.  Autophagy is required to maintain muscle mass. , 2009, Cell metabolism.

[37]  P. Austin.  Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples , 2009, Statistics in medicine.

[38]  G. Frühbeck,et al.  Leptin Administration Favors Muscle Mass Accretion by Decreasing FoxO3a and Increasing PGC-1α in ob/ob Mice , 2009, PloS one.

[39]  A. Hine,et al.  Expression of the ubiquitin-proteasome pathway and muscle loss in experimental cancer cachexia , 2005, British Journal of Cancer.

[40]  D. Mann,et al.  TNF-acts via p 38 MAPK to stimulate expression of the ubiquitin ligase atrogin 1 / MAFbx in skeletal muscle , 2005 .

[41]  Yoshinao Abe,et al.  Impairment of host resistance to Listeria monocytogenes infection in liver of db/db and ob/ob mice. , 2005, Diabetes.

[42]  I. Kettelhut,et al.  Role of ubiquitin‐proteasome‐dependent proteolytic process in degradation of muscle protein from diabetic rabbits , 2001, Molecular and Cellular Biochemistry.

[43]  E. Miska,et al.  Differential localization of HDAC4 orchestrates muscle differentiation. , 2001, Nucleic acids research.

[44]  G. Fantuzzi,et al.  Leptin deficiency enhances sensitivity to endotoxin-induced lethality. , 1999, American journal of physiology. Regulatory, integrative and comparative physiology.

[45]  C. Mantzoros,et al.  Role of leptin in the neuroendocrine response to fasting , 1996, Nature.

[46]  J. Wang,et al.  Energy-ubiquitin-dependent muscle proteolysis during sepsis in rats is regulated by glucocorticoids. , 1996, The Journal of clinical investigation.