Obesity does not Lead to Imbalance Between Myocardial Phospholamban Phosphorylation and Dephosphorylation

Abstract

Background The activation of the beta-adrenergic system promotes G protein stimulation that, via cyclic adenosine monophosphate (cAMP), alters the structure of protein kinase A (PKA) and leads to phospholamban (PLB) phosphorylation. This protein participates in the system that controls intracellular calcium in muscle cells, and it is the primary regulator of sarcoplasmic reticulum calcium pump activity. In obesity, the beta-adrenergic system is activated by the influence of increased leptin, therefore, resulting in higher myocardial phospholamban phosphorylation via cAMP-PKA. Objective To investigate the involvement of proteins which regulate the degree of PLB phosphorylation due to beta-adrenergic activation in obesity. In the present study, we hypothesized that there is an imbalance between phospholamban phosphorylation and dephosphorylation, with prevalence of protein phosphorylation. Methods Male Wistar rats were randomly distributed into two groups: control (n = 14), fed with normocaloric diet; and obese (n = 13), fed with a cycle of four unsaturated high-fat diets. Obesity was determined by the adiposity index, and protein expressions of phosphatase 1 (PP-1), PKA, PLB, phosphorylated phospholamban at serine16 (PPLB-Ser16) were assessed by Western blot. Results Obesity caused glucose intolerance, hyperinsulinemia, hypertriglyceridemia, hyperleptinemia and did not alter the protein expression of PKA, PP-1, PLB, PPLB-Ser16. Conclusion Obesity does not promote an imbalance between myocardial PLB phosphorylation and dephosphorylation via beta-adrenergic system.

Saturated high-fat diet-induced obesity increases adenylate cyclase of myocardial β -adrenergic system and does not compromise cardiac function

“…Minhas et al (2005) evidenced, in ob/ob mice, a decrease in Gas protein expression and PKA activity, which have been restored after exogenous administration of leptin, suggesting the participation of deficiency of this hormone. Different authors have observed that the protein expression and activity of PKA did not change in dietary obesity model (Moberly et al 2013;Freire et al 2014), corroborating our data. Overall, the discrepancy in these findings seems to be associated with the use of genetic models of obesity, exposure time to high-fat diet or, even with the dietary composition.…”

“…; Freire et al. ), corroborating our data. Overall, the discrepancy in these findings seems to be associated with the use of genetic models of obesity, exposure time to high‐fat diet or, even with the dietary composition.…”

Disfunção cardíaca induzida por obesidade genética e dietética: modulação pelo trânsito de cálcio

“…É importante ressaltar que Freire et al 30 utilizando ratos Wistar sob as mesmas condições dos estudos citados no parágrafo anterior não encontraram desequilíbrio entre a fosforilação e desfosforilação do PLB na serina 16. Os autores propõem que o grau de obesidade dos animais pode ter influenciado nos resultados encontrados.…”

Cardiac function and intracellular Ca2+ handling proteins are not impaired by high-saturated-fat diet-induced obesity

“…Regarding the myocardial proteins analysis related to the intracellular Ca 2+ handling, obesity did not induce significant changes in the molecules analyzed. Most of the studies found in the literature on this subject used models of obesity induced by high-fat diets rich in unsaturated fatty acids and the results are divergent, probably due to differences in experimental protocols (9,14 –18,32). As mentioned previously, Cheng et al (19), using a high-saturated-fat diet in male Wistar rats for 8 weeks, showed that only pPLB Thr 17 /PLB ratio was downregulated, despite no evidence of left ventricular dysfunction or remodeling.…”