Clinical research study
Dramatic Reversal of Derangements in Muscle Metabolism and Left Ventricular Function After Bariatric Surgery

https://doi.org/10.1016/j.amjmed.2008.06.033Get rights and content

Abstract

Objective

The study objective was to define muscle metabolic and cardiovascular changes after surgical intervention in clinically severe obese patients.

Methods

Obesity is a state of metabolic dysregulation that can lead to maladaptive changes in heart and skeletal muscle, including insulin resistance and heart failure. In a prospective longitudinal study, 43 consecutive patients underwent metabolic profiling, skeletal muscle biopsies, and resting echocardiograms at baseline and 3 and 9 months after bariatric surgery.

Results

Body mass index decreased (mean changes, 95% confidence interval [CI]): 7.7 kg/m2 (95% CI, 6.70-8.89) at 3 months and 5.6 kg/m2 (95% CI, 4.45-6.80; P < .0001) at 9 months after surgery, with restoration of insulin sensitivity and decreases in plasma leptin at the same time points. Concurrent with these changes were dramatic decreases in skeletal muscle transcript levels of stearoyl coenzyme-A desaturase and pyruvate dehydrogenase kinase-4 at 3 and 9 months (P < .0001, for both) and a significant decrease in peroxisome proliferation activated receptor-α–regulated genes at 9 months. Left ventricular relaxation impairment, assessed by tissue Doppler imaging, normalized 9 months after surgery.

Conclusion

Weight loss results in the reversal of systemic and muscle metabolic derangements and is accompanied by a normalization of left ventricular diastolic function.

Section snippets

Subject Selection

We offered participation to patients of any race/ethnicity from the University of Texas Houston Bariatric Surgery Center who met the inclusion criteria for bariatric surgery outlined previously.13 Exclusion criteria were coronary artery disease, ischemic cardiomyopathy, severe peripheral vascular disease, a current history of smoking, pregnancy, or an age of less than 18 years. The study was approved by the Committee for the Protection Human Subjects at The University of Texas Health Science

Preoperative Findings

Table 1 lists the baseline characteristics of all patients, the patients undergoing SPGB, and the patients undergoing LAGB. There were no significant differences in the baseline characteristics between the 2 surgical groups for any of the variables measured. Patients had more fat mass than lean body mass at baseline, as measured by bioelectrical impedance analysis (Table 1). Mean blood pressure and heart rates were in the normal range. Almost all of the patients met criteria for insulin

Discussion

The main findings of our study are that weight loss induced by surgery is accompanied by a reversal of insulin resistance and dramatic changes in skeletal muscle metabolism. The former findings were expected, but the latter findings are new. Adipose tissue is an active endocrine organ, and an increased adipose mass is associated with insulin resistance and alterations of fatty acid oxidation by complex mechanisms.22, 23 These effects are mediated by adipose-derived hormones and cytokines (eg,

Limitations

We are excited about the findings, but we also are aware of the following limitations. First, this is a small prospective, longitudinal observational study, and we can only infer a relationship between the outcomes, not prove a causal relationship. Larger studies using external controls are needed to define the true relationships among skeletal muscle gene expression, systemic metabolism, and contractile function of the heart. Second, gene expression does not necessarily reflect protein content

Conclusions

Nonpharmacologic weight loss induced by bariatric surgery results in an early reversal of the maladaptive responses to obesity. Leptin resistance and insulin resistance reverse, leading to improved systemic metabolism and skeletal muscle gene expression. It is possible that these mechanisms also may exert a positive effect on left ventricular diastolic function. The implications of these findings for freedom from comorbidities of obesity remain to be substantiated by the long-term follow-up of

Acknowledgments

The authors acknowledge the following contributors: Carol Wolin-Riklin, RN, University of Texas at Houston General Clinical Research Center, and Charles Majka, BS, University of Texas Houston Medical School for data collection; Rebecca L. Salazar, BS, University of Texas Houston Medical School Department of Medicine, for technical assistance. We thank Roxy A. Tate for expert editorial help.

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    Supported by the National Heart, Lung, and Blood Institute of the US Public Health Service (R01HL73162 and M01 RR02558). None of the authors of this work have any financial conflicts of interest to disclose. All authors had access to the data and a role in writing the article.

    Clinical Trials Registry: ClinicalTrials.gov Identifier: NCT00178633; http:/www.clinicaltrials.gov

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