RESUMO
NEW FINDINGS: What is the central question of this study? Does vascular endothelial growth factor (VEGF) expressed by both endothelial cells and skeletal myofibres maintain the number of skeletal muscle capillaries and regulate endurance exercise? What is the main finding and its importance? VEGF expressed by both endothelial cells and skeletal myofibres is not essential for maintaining capillary number but does contribute to exercise performance. ABSTRACT: Many chronic diseases lead to exercise intolerance, with loss of skeletal muscle capillaries. While many muscle cell types (myofibres, satellite cells, endothelial cells, macrophages and fibroblasts) express vascular endothelial growth factor (VEGF), most muscle VEGF is stored in myofibre vesicles which can release VEGF to signal VEGF receptor-expressing cells. VEGF gene ablation in myofibres or endothelial cells alone does not cause capillary regression. We hypothesized that simultaneously deleting the endothelial cell (EC) and skeletal myofibre (Skm) VEGF gene would cause capillary regression and impair exercise performance. This was tested in adult mice by simultaneous conditional deletion of the VEGF gene (Skm/EC-VEGF-/- mice) through the use of VEGFLoxP, HSA-Cre-ERT2 and PDGFb-iCre-ERT2 transgenes. These double-deletion mice were compared to three control groups - WT, EC VEGF gene deletion alone and myofibre VEGF gene deletion alone. Three weeks after initiating gene deletion, Skm/EC-VEGF-/- mice, but not SkmVEGF-/- or EC-VEGF-/- mice, reached exhaustion 40 min sooner than WT mice in treadmill tests (P = 0.002). WT, SkmVEGF-/- and EC-VEGF-/- , but not Skm/EC-VEGF-/- , mice gained weight over the 3 weeks. Capillary density, fibre area and capillary: fibre ratio in soleus, plantaris, gastrocnemius and cardiac papillary muscle were similar across the groups. Phosphofructokinase and pyruvate dehydrogenase activities increased only in Skm/EC-VEGF-/- mice. These data suggest that deletion of the VEGF gene simultaneously in endothelial cells and myofibres, while reducing treadmill endurance and despite compensatory augmentation of glycolysis, is not required for muscle capillary maintenance. Reduced endurance remains unexplained, but may possibly be related to a role for VEGF in controlling perfusion of contracting muscle.
Assuntos
Capilares/fisiologia , Células Endoteliais/fisiologia , Inativação Gênica/fisiologia , Fibras Musculares Esqueléticas/fisiologia , Condicionamento Físico Animal/fisiologia , Fatores de Crescimento do Endotélio Vascular/genética , Animais , Capilares/metabolismo , Células Endoteliais/metabolismo , Teste de Esforço/métodos , Masculino , Camundongos , Contração Muscular/genética , Fibras Musculares Esqueléticas/metabolismo , Miocárdio/metabolismo , Neovascularização Fisiológica/genéticaRESUMO
BACKGROUND: No studies have evaluated the effect of metabolic and bariatric surgery (MBS) on nonalcoholic fatty liver disease (NAFLD) and cardiometabolic markers in metabolically healthy patients with morbid obesity (MHMO) at midterm. OBJECTIVES: To assess the effect of MBS on NAFLD and cardiometabolic markers in MHMO patients and ascertain whether metabolically unhealthy patients with morbid obesity (MUMO) remain metabolically healthy at 5 years after MBS. SETTING: University hospital. METHODS: A total of 191 patients with a body mass index >40 kg/m2 and at least 5 years of follow-up were retrospectively analyzed. Lost to follow-up were 37.6% (151 of 401 patients). Patients were classified as MHMO if 1 or 0 of the cardiometabolic markers were present using the Wildman criteria. The degree of liver fibrosis was assessed using the NAFLD fibrosis score (NFS). RESULTS: Forty-one patients (21.5%) fulfilled the criteria for MHMO. They showed significant improvements in blood pressure (from 135.1 ± 22.1 and 84.2 ± 14.3 mm Hg to 117.7 ± 19.2 and 73.0 ± 10.9 mm Hg), plasma glucose (from 91.0 ± 5.6 mg/dL to 87.2 ± 5.2 mg/dL), homeostatic model assessment for insulin resistance (from 2.2 ± .9 to 1.0 ± .8), triglycerides (from 88.0 [range, 79.5-103.5] mg/dL to 61.0 [range, 2.0-76.5] mg/dL), alanine aminotransferase, gamma-glutamyl transpeptidase NFS (from -1.0 ± 1.0 to -1.9 ± 1.2), and high-density lipoprotein cholesterol (from 56.9 ± 10.5 mg/dL to 77.9 ± 17.4 mg/dL) at 5 years after surgery. A total of 108 MUMO patients (84.4%) who became metabolically healthy after 1 year stayed healthy at 5 years. CONCLUSIONS: MBS induced a midterm improvement in cardiometabolic and NAFLD markers in MHMO patients. Seventy-six percent of MUMO patients became metabolically healthy at 5 years after MBS.
Assuntos
Cirurgia Bariátrica , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Índice de Massa Corporal , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/cirurgia , Obesidade Mórbida/complicações , Obesidade Mórbida/metabolismo , Obesidade Mórbida/cirurgia , Estudos RetrospectivosRESUMO
To ascertain the 5-year metabolic effects of bariatric surgery in poor weight loss (WL) responders and establish associated factors. METHODS: Retrospective analysis of a non-randomised prospective cohort of bariatric surgery patients completing a 5-year follow-up. Mid-term poor WL was considered when 5-year excess weight loss was <50%. RESULTS: Forty-three (20.3%) of the 212 included patients were mid-term poor WL responders. They showed an improvement in all metabolic markers at 2 years, except for total cholesterol. This improvement with respect to baseline was maintained at 5 years for plasma glucose, HbA1c, HOMA, HDL and diastolic blood pressure; however, LDL cholesterol, triglycerides and systolic blood pressure were similar to presurgical values. Comorbidity remission rates were comparable to those obtained in the good WL group except for hypercholesterolaemia (45.8% vs. poor WL, p = 0.005). On multivariate analysis, lower baseline HDL cholesterol levels, advanced age and lower preoperative weight loss were independently associated with poor mid-term WL. CONCLUSIONS: Although that 1 in 5 patients presented suboptimal WL 5 years after bariatric surgery, other important metabolic benefits were maintained.