ABSTRACT
Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic efficacy of the β 3-adrenergic receptor agonist Mirabegron and FGF21. Additionally, combing those molecules with the Cx43 gap junction channel activator danegaptide shows a similar enhanced efficacy. In light of these findings, we propose a model in which connecting adipocytes via Cx43 gap junction channels primes adipose tissue to pharmacological agents designed to engage it. Thus, Cx43 gap junction activators hold great potential for combination with additional agents targeting adipose tissue.
ABSTRACT
Objective To investigate the nutritional status of patients with heart failure and its effect on all-cause mortality.Methods A total of 351 patients with chronic heart failure,who were consecutively admitted to the East Hospital of Shanghai from March 2013 to November 2015,were put into the heart failure with reduced left ventricular ejection fraction (HFrEF) group.They were compared to 222 controls who were admitted during the same period for preclinical heart failure.After a median follow-up time of 606 days,108 patients of the HFrEF group died,compared to 11 of the controls.Logistic regression was used to analyze correlations of all-cause mortality with the patients' body mass index (BMI),serum albumin and other factors.Results Compared to the controls,patients with chronic heart failure had lower BMI [(22.71±3.95) kg/m2 vs.(24.23±3.66) kg/m2,t=4.331,P=0.000],total cholesterol [(3.81±0.99) mmol/L vs.(4.03±0.96) mmol/L,t=2.638,P=0.009],albumin [(38.18±5.03) g/Lvs.(40.18±6.12) g/L,t=3.874,P=0.000] and prealbumin [(187.67±61.83) mg/L vs.(211.94±65.44) mg/L,t=3.937,P=0.000].Within the HFrEF group,patients with lower BMI had higher mortality (36.0％ vs.22.4％,P=0.008).Logistic regression suggested BMI,age were independent predictors of all-cause death.Conclusions Patients with chronic heart failure had high incidence of malnutrition,and those with BMI＜22 kg/m2 had higher risk of mortality.Serum albumin and BMI not only reflected nutritional status of the patients but had significant implications on prognosis.