Obesity attenuates inflammation, protein catabolism, dyslipidaemia, and muscle weakness during sepsis, independent of leptin
Abstract Background 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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-02-01
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| Series: | Journal of Cachexia, Sarcopenia and Muscle |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jcsm.12904 |
| _version_ | 1797826763561107456 |
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| author | Wouter Vankrunkelsven Sarah Derde Jan Gunst Sarah Vander Perre Emiel Declerck Lies Pauwels Inge Derese Greet Van den Berghe Lies Langouche |
| author_facet | Wouter Vankrunkelsven Sarah Derde Jan Gunst Sarah Vander Perre Emiel Declerck Lies Pauwels Inge Derese Greet Van den Berghe Lies Langouche |
| author_sort | Wouter Vankrunkelsven |
| collection | DOAJ |
| description | Abstract Background 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. Methods In a mouse model of sepsis, we investigated the effects of genetic leptin inactivation in obese mice (leptin‐deficient obese mice vs. diet‐induced obese mice) and of leptin supplementation in lean mice (n = 110). We assessed impact on survival, body weight and composition, markers of muscle wasting and weakness, inflammation, and lipid metabolism. In human lean and overweight/obese intensive care unit (ICU) patients, we assessed markers of protein catabolism (n = 1388) and serum leptin (n = 150). Results Sepsis mortality was highest in leptin‐deficient obese mice (53% vs. 23% in diet‐induced obese mice and 37% in lean mice, P = 0.03). Irrespective of leptin, after 5 days of sepsis, lean mice lost double the amount of lean body mass than obese mice (P < 0.0005). Also, irrespective of leptin, obese mice maintained specific muscle force up to healthy levels (P = 0.3) whereas lean mice suffered from reduced specific muscle force (72% of healthy controls, P < 0.0002). As compared with lean septic mice, both obese septic groups had less muscle atrophy, liver amino acid catabolism, and inflammation with a 50% lower plasma TNFα increase (P < 0.005). Conversely, again mainly irrespective of leptin, obese mice lost double amount of fat mass than lean mice after 5 days of sepsis (P < 0.0001), showed signs of increased lipolysis and ketogenesis, and had higher plasma HDL and LDL lipoprotein concentrations (P ≤ 0.01 for all). Muscle fibre type composition was not altered during sepsis, but a higher atrophy sensitivity of type IIb fibres compared with IIa and IIx fibres was observed, independent of obesity or leptin. After 5 days of critical illness, serum leptin was higher (P < 0.0001) and the net waste of nitrogen (P = 0.006) and plasma urea‐to‐creatinine ratio (P < 0.0001) was lower in overweight/obese compared with lean ICU human patients. Conclusions Leptin did not mediate the protective effect of obesity against sepsis‐induced muscle wasting and weakness in mice. Instead, obesity—independent of leptin—attenuated inflammation, protein catabolism, and dyslipidaemia, pathways that may play a role in the observed muscle protection. |
| first_indexed | 2024-04-09T12:37:26Z |
| format | Article |
| id | doaj.art-43b275e2b3d14532b76a60821f72697a |
| institution | Directory Open Access Journal |
| issn | 2190-5991 2190-6009 |
| language | English |
| last_indexed | 2024-04-09T12:37:26Z |
| publishDate | 2022-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Cachexia, Sarcopenia and Muscle |
| spelling | doaj.art-43b275e2b3d14532b76a60821f72697a2023-05-15T09:27:15ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092022-02-0113141843310.1002/jcsm.12904Obesity attenuates inflammation, protein catabolism, dyslipidaemia, and muscle weakness during sepsis, independent of leptinWouter Vankrunkelsven0Sarah Derde1Jan Gunst2Sarah Vander Perre3Emiel Declerck4Lies Pauwels5Inge Derese6Greet Van den Berghe7Lies Langouche8Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine KU Leuven Leuven BelgiumClinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine KU Leuven Leuven BelgiumClinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine KU Leuven Leuven BelgiumClinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine KU Leuven Leuven BelgiumClinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine KU Leuven Leuven BelgiumClinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine KU Leuven Leuven BelgiumClinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine KU Leuven Leuven BelgiumClinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine KU Leuven Leuven BelgiumClinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine KU Leuven Leuven BelgiumAbstract Background 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. Methods In a mouse model of sepsis, we investigated the effects of genetic leptin inactivation in obese mice (leptin‐deficient obese mice vs. diet‐induced obese mice) and of leptin supplementation in lean mice (n = 110). We assessed impact on survival, body weight and composition, markers of muscle wasting and weakness, inflammation, and lipid metabolism. In human lean and overweight/obese intensive care unit (ICU) patients, we assessed markers of protein catabolism (n = 1388) and serum leptin (n = 150). Results Sepsis mortality was highest in leptin‐deficient obese mice (53% vs. 23% in diet‐induced obese mice and 37% in lean mice, P = 0.03). Irrespective of leptin, after 5 days of sepsis, lean mice lost double the amount of lean body mass than obese mice (P < 0.0005). Also, irrespective of leptin, obese mice maintained specific muscle force up to healthy levels (P = 0.3) whereas lean mice suffered from reduced specific muscle force (72% of healthy controls, P < 0.0002). As compared with lean septic mice, both obese septic groups had less muscle atrophy, liver amino acid catabolism, and inflammation with a 50% lower plasma TNFα increase (P < 0.005). Conversely, again mainly irrespective of leptin, obese mice lost double amount of fat mass than lean mice after 5 days of sepsis (P < 0.0001), showed signs of increased lipolysis and ketogenesis, and had higher plasma HDL and LDL lipoprotein concentrations (P ≤ 0.01 for all). Muscle fibre type composition was not altered during sepsis, but a higher atrophy sensitivity of type IIb fibres compared with IIa and IIx fibres was observed, independent of obesity or leptin. After 5 days of critical illness, serum leptin was higher (P < 0.0001) and the net waste of nitrogen (P = 0.006) and plasma urea‐to‐creatinine ratio (P < 0.0001) was lower in overweight/obese compared with lean ICU human patients. Conclusions Leptin did not mediate the protective effect of obesity against sepsis‐induced muscle wasting and weakness in mice. Instead, obesity—independent of leptin—attenuated inflammation, protein catabolism, and dyslipidaemia, pathways that may play a role in the observed muscle protection.https://doi.org/10.1002/jcsm.12904LeptinCritical illnessSepsisMuscle weaknessIntensive care unit acquired weaknessAtrophy |
| spellingShingle | Wouter Vankrunkelsven Sarah Derde Jan Gunst Sarah Vander Perre Emiel Declerck Lies Pauwels Inge Derese Greet Van den Berghe Lies Langouche Obesity attenuates inflammation, protein catabolism, dyslipidaemia, and muscle weakness during sepsis, independent of leptin Journal of Cachexia, Sarcopenia and Muscle Leptin Critical illness Sepsis Muscle weakness Intensive care unit acquired weakness Atrophy |
| title | Obesity attenuates inflammation, protein catabolism, dyslipidaemia, and muscle weakness during sepsis, independent of leptin |
| title_full | Obesity attenuates inflammation, protein catabolism, dyslipidaemia, and muscle weakness during sepsis, independent of leptin |
| title_fullStr | Obesity attenuates inflammation, protein catabolism, dyslipidaemia, and muscle weakness during sepsis, independent of leptin |
| title_full_unstemmed | Obesity attenuates inflammation, protein catabolism, dyslipidaemia, and muscle weakness during sepsis, independent of leptin |
| title_short | Obesity attenuates inflammation, protein catabolism, dyslipidaemia, and muscle weakness during sepsis, independent of leptin |
| title_sort | obesity attenuates inflammation protein catabolism dyslipidaemia and muscle weakness during sepsis independent of leptin |
| topic | Leptin Critical illness Sepsis Muscle weakness Intensive care unit acquired weakness Atrophy |
| url | https://doi.org/10.1002/jcsm.12904 |
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