Long-term obesity promotes alterations in diastolic function induced by reduction of phospholamban phosphorylation at serine-16 without affecting calcium handling

Abstract

Few studies have evaluated the relationship between the duration of obesity, cardiac function, and the proteins involved in myocardial calcium (Ca(2+)) handling. We hypothesized that long-term obesity promotes cardiac dysfunction due to a reduction of expression and/or phosphorylation of myocardial Ca(2+)-handling proteins. Thirty-day-old male Wistar rats were distributed into two groups (n = 10 each): control (C; standard diet) and obese (Ob; high-fat diet) for 30 wk. Morphological and histological analyses were assessed. Left ventricular cardiac function was assessed in vivo by echocardiographic evaluation and in vitro by papillary muscle. Cardiac protein expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a), calsequestrin, L-type Ca(2+) channel, and phospholamban (PLB), as well as PLB serine-16 phosphorylation (pPLB Ser(16)) and PLB threonine-17 phosphorylation (pPLB Thr(17)) were determined by Western blot. The adiposity index was higher (82%) in Ob rats than in C rats. Obesity promoted cardiac hypertrophy without alterations in interstitial collagen levels. Ob rats had increased endocardial and midwall fractional shortening, posterior wall shortening velocity, and A-wave compared with C rats. Cardiac index, early-to-late diastolic mitral inflow ratio, and isovolumetric relaxation time were lower in Ob than in C. The Ob muscles developed similar baseline data and myocardial responsiveness to increased extracellular Ca(2+). Obesity caused a reduction in cardiac pPLB Ser(16) and the pPLB Ser(16)/PLB ratio in Ob rats. Long-term obesity promotes alterations in diastolic function, most likely due to the reduction of pPLB Ser(16), but does not impair the myocardial Ca(2+) entry and recapture to SR.

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

“…; Lima‐Leopoldo et al. ). However, echocardiographic structural study showed increased atrial dimension in the obese group that was not accompanied by other anatomical modifications.…”

The influence of obesity by a diet high in saturated fats and carbohydrates balance in the manifestation of systemic complications and comorbidities

“…The effectiveness of dietary model is attributed to the greater feed efficiency in obese animals probably due to the thermal effect of fat, since this nutrient requires less energy (2-3%) to be absorbed and digested, making it easily stored as triglycerides in adipocytes [6,17,26]. The current study showed that obese animals had numerous complications and absence of comorbidities.…”

“…However, in this study, this type of carbohydrate was not used, since this would not allow knowing if the manifestation of the complications and comorbidities would be exclusively due to the increase of the amount of fat or its association with a carbohydrate with harmful capacity. It is believed that other factors may also have influenced this result as time of exposure to diet, fat percentage, and type (saturated or unsaturated) and source (animal or vegetable) of fatty acids and animal model [6,17,18,30,33,[35][36][37].…”

“…It is not well defined what would be the most appropriate diet to build up the triad in experimental models: obesity complications, and comorbidities. For this purpose, several authors use diets rich in fatty acids [14][15][16][17][18]. In diets using predominantly unsaturated fat, the rodents develop obesity and different types of complications associated, whereas comorbidities are not common manifestations [19,20].…”

“…When there is a preponderance of saturated fatty acids, both abnormalities are more constant, by raising total cholesterol and LDL cholesterol, which causes deposition in the arteries in the heart and other parts of the body besides triggering obesity and overweight [14,21,22]. However, diets that use high fat content result in a decrement of other nutrients, such as carbohydrate, in order to maintain an appropriate proportion of dietary constituents [6,17,18]. Due to the reduction in energy availability from carbohydrates, the fat becomes the main source of energy, which could cause a decrease in fat deposits and attenuates the pathogenic events associated with obesity [23].…”