Bariatric surgery to unload the stressed heart: a metabolic hypothesis

Abstract

Obesity is an independent risk factor for cardiovascular disease. Data from the Framingham Study have reported a higher incidence of heart failure in obese individuals compared with a normal cohort. The body initially copes with the abundance of fuel present in an obese milieu by storing it in adipose tissue. However, when the storage capacity is exceeded, the excess energy is taken up and stored ectopically as fat in vital organs such as the heart. Indeed, intramyocardial lipid overload is present in hearts of obese patients, as well as in hearts of animal models of obesity, and is associated with a distinct gene expression profile and cardiac dysfunction. By imposing a metabolic stress on the heart, obesity causes it to hypertrophy and ultimately to fail. Conventional measures to treat obesity include diet, exercise, and drugs. More recently, weight loss surgery (WLS) has achieved increasing prominence because of its ability to reduce the neurohumoral load, normalize metabolic dysregulation, and improve overall survival. The effects of WLS on systemic metabolic, neurohumoral, and hemodynamic parameters are well described and include an early normalization of serum glucose and insulin levels as well as reduction in blood pressure. WLS is also associated with reverse cardiac remodeling, regression of left ventricular hypertrophy, and improved left ventricular and right ventricular function. By targeting the source of the excess energy, we hypothesize that WLS improves contractile function by limiting exogenous substrate availability to the metabolically overloaded heart. These changes have also been found to be associated with increased levels of adiponectin and improved insulin sensitivity. Taken together, the sustained beneficial effects of WLS on left ventricular mass and function highlight the need to better understand the mechanism by which obesity regulates cardiovascular physiology.

Fig. 1.

Proposed relationship of the exposome, susceptibility to allostatic pressure, and increased load on the heart in obesity. The exposome encompasses the genetic and epigenetic factors that dictate an individual's susceptibility to allostatic pressure. When an individual's ability to reestablish homeostatic equilibrium (allostasis) is exceeded, the heart is subjected to increased hemodynamic, neurohormonal, and metabolic load, and heart disease ensues.

Fig. 2.

Representative oil-red-O stain of vastus lateralis biopsy sample and mRNA transcript levels of pyruvate dehydrogenase kinase 4 (pdk4) and human stearoyl CoA desaturase 1 (scd-1) in obese patients at baseline, 3 mo , and 9 mo after bariatric surgery. Top: oil-red-O staining at baseline and 3 and 9 mo after surgery (P < 0.009). Bottom: mRNA transcript levels of pdk4 and scd-1 at baseline and after surgery (P < 0.001). Permission was obtained to reuse figure art from Leichman et al. (48).

Fig. 3.

Fractional change in left ventricular mass (LVM) and metabolic markers of obesity up to 24 months after bariatric surgery. The decrease in LVM was linear, whereas the decrease in metabolic markers of obesity stabilized after 9 months. HOMA-IR, homeostasis model assessment of insulin resistance; CRP, C-reactive protein. Permission was obtained to reuse figure art from Algahim et al. (2).