Can Adiponectin Help us to Target Diastolic Dysfunction?

Abstract

Adiponectin is the most abundant adipokine and exhibits anti-inflammatory, antiatherogenic and antidiabetic properties. Unlike other adipokines, it inversely correlates with body weight and obesity-linked cardiovascular complications. Diastolic dysfunction is the main mechanism responsible for approximately half of all heart failure cases, the so-called heart failure with preserved ejection fraction (HFpEF), but therapeutic strategies specifically directed towards these patients are still lacking. In the last years, a link between adiponectin and diastolic dysfunction has been suggested. There are several mechanisms through which adiponectin may prevent most of the pathophysiologic mechanisms underlying diastolic dysfunction and HFpEF, including the prevention of myocardial hypertrophy, cardiac fibrosis, nitrative and oxidative stress, atherosclerosis and inflammation, while promoting angiogenesis. Thus, understanding the mechanisms underlying adiponectin-mediated improvement of diastolic function has become an exciting field of research, making adiponectin a promising therapeutic target. In this review, we explore the relevance of adiponectin signaling for the prevention of diastolic dysfunction and identify prospective therapeutic targets aiming at the treatment of this clinical condition.

Targeting Obesity and Diabetes to Treat Heart Failure with Preserved Ejection Fraction

“…Animal studies have shown that adiponectin can inhibit cardiac hypertrophy and fibrosis, and reduce infarct size (174). Together these findings support the supposition that adiponectin might have therapeutic potential in HFpEF patients (176). However, circulating adiponectin levels are increased in both HFrEF and HFpEF (177).…”

“…Adiponectin is the major adipokine produced by adipose tissue with anti-inflammatory, antidiabetic, anti-apoptotic, and anti-atherogenic properties (174, 176). Circulating adiponectin levels are decreased in obesity and type 2 diabetes and downregulation of adiponectin and its receptors is associated with insulin resistance and diabetes, as well as increased risk of HTN and coronary artery disease (174, 176). Animal studies have shown that adiponectin can inhibit cardiac hypertrophy and fibrosis, and reduce infarct size (174).…”

“…Low adiponectin was associated with higher odds of indices of diastolic dysfunction in women, but lower odds in men, and lower adiponectin was associated with increased left ventricular mass only in women (179). Other variables that may come into play are adiponectin receptor desensitization, receptor subtypes, and the different-size molecular weight complexes of circulating adiponectin (“isoforms”) (176). …”

Concentración de adiponectina posterior a reducción de masa corporal en un grupo de mujeres obesas premenopáusicas en Lima, Perú

“…Dentro de las variables bioquímicas evaluadas era esperado encontrar a la glucosa como biomarcador de obesidad debido a que esta enfermedad también se encuentra relacionada con el desarrollo de diabetes tipo 2 (29) . La adiponectina, que constituye el 0,01 % al 0,05 % de todas las proteínas circulantes en plasma (7,8) , existe como monómero, trímero de bajo peso molecular (LMW), hexámero de mediano peso molecular (MMW) y como multímero de alto peso molecular (HMW) que comprende al menos 18 monómeros (26,30,31) . Sin embargo, parece que la combinación de HMW y MMW es la más relevante en la respuesta inflamatoria ya que esta combinación incrementa la liberación de interleucina-6, interleucina-8 y la metaloproteinasa MMP-3 (32) .…”

“…De hecho, algunas investigaciones tienen como objetivo el estudio de la administración exógena de adiponectina y su efecto en el mejoramiento de la condición del paciente (9,21,22) , no solo en enfermedades metabólicas, sino también en distrofia muscular de Duchenne (23) o mal de Alzheimer (24) . Revisiones y metaanálisis recientes encuentran algunas discrepancias entre estudios con respecto al uso de adiponectina como un biomarcador de enfermedades metabólicas por lo que todavía se recomienda incrementar el número de investigaciones de modo que este aspecto pueda ser aclarado (7,13,19,25,26) .…”