RESUMEN
Two thirds of heart failure (HF) patients are overweight or obese. Current guidelines are unclear about weight reduction goals. We explored impact of Heartful Living (HL,) a cardiologist-led Self-Inquiry (Si) mindfulness program targeting deeper insight and resilience to promote intentional weight loss in morbidly obese HF patients. The primary outcome was >10% intentional weight loss in HF achieved in 6 males and 4 females, BMI 40 (± 8.11)Kg/m2, age of 67.1 (± 10.02) years, who participated in HL and were followed for 10 months to 3 years. Two patients had systolic dysfunction, with a reduced ejection fraction of 25 and 40%. All had diabetes (7) or metabolic syndrome (3). The fasting was unsupervised, at home and intuitive without prespecified parameters. The average weight loss through HUGE fasting was 17.5% of total body weight for all 10 patients, and 25.5% for the 5 patients followed over 2 years. Diabetes, hypertension and renal parameters improved allowing reduction of medications. This prospective case series followed ten morbidly obese patients with HF, and demonstrates intentional weight loss can be achieved with mindfulness. Clinical improvement occurs when HF patients reach over 15% weight loss. Prospective studies are needed to evaluate outcomes in broader HF populations.
RESUMEN
Vacuolar protein sorting 1 (Vps1), the yeast homolog to human dynamin, is a GTP hydrolyzing protein, which plays an important role in protein sorting and targeting between the Golgi and late endosomal compartments. In this study, we assessed the functional significance of Vps1 in the membrane traffic towards the vacuole. We show here that vps1 delta cells accumulated FM4-64 to a greater extent than wild-type (WT))cells, suggesting slower endocytic degradation traffic toward the vacuole. In addition, we observed that two endosome-to-vacuole traffic markers, DsRed-FYVE and Ste2-GFP, were highly accumulated in Vps1-deficient cells, further supporting Vps1's implication in efficient trafficking of endocytosed materials to the vacuole. Noteworthy, a simultaneous imaging analysis in conjunction with FM4-64 pulse-chase experiment further revealed that Vps1 plays a role in late endosome to the vacuole transport. Consistently, our subcellular localization analysis showed that Vps1 is present at the late endosome. The hyperaccumulation of endosomal intermediates in the vps1 mutant cells appears to be caused by the disruption of integrity of HOPS tethering complexes, manifested by mislocalization of Vps39 to the cytoplasm. Finally, we postulate that Vps1 functions together with the Endosomal Sorting Complex Required for Transport (ESCRT) complex at the late endosomal compartments, based on the observation that the double mutants, in which VPS1 along with singular ESCRT I, II and III genes have been disrupted, exhibited synthetic lethality. Together, we propose that Vps1 is required for correct and efficient trafficking from the late endosomal compartments to the vacuole.