Effect of Incorporating 1 Avocado Per Day Versus Habitual Diet on Visceral Adiposity: A Randomized Trial.

Background Excess visceral adiposity is associated with increased risk of cardiometabolic disorders. Short-term well-controlled clinical trials suggest that regular avocado consumption favorably affects body weight, visceral adiposity, and satiety. Methods and Results The HAT Trial (Habitual Diet and Avocado Trial) was a multicenter, randomized, controlled parallel-arm trial designed to test whether consuming 1 large avocado per day for 6 months in a diverse group of free-living individuals (N=1008) with an elevated waist circumference compared with a habitual diet would decrease visceral adiposity as measured by magnetic resonance imaging. Secondary and additional end points related to risk factors associated with cardiometabolic disorders were assessed. The primary outcome, change in visceral adipose tissue volume during the intervention period, was not significantly different between the Avocado Supplemented and Habitual Diet Groups (estimated mean difference (0.017 L [-0.024 L, 0.058 L], P=0.405). No significant group differences were observed for the secondary outcomes of hepatic fat fraction, hsCRP (high-sensitivity C-reactive protein), and components of the metabolic syndrome. Of the additional outcome measures, modest but nominally significant reductions in total and low-density lipoprotein cholesterol were observed in the Avocado Supplemented compared with the Habitual Diet Group. Changes in the other additional and post hoc measures (body weight, body mass index, insulin, very low-density lipoprotein concentrations, and total cholesterol:high-density lipoprotein cholesterol ratio) were similar between the 2 groups. Conclusions Addition of 1 avocado per day to the habitual diet for 6 months in free-living individuals with elevated waist circumference did not reduce visceral adipose tissue volume and had minimal effect on risk factors associated with cardiometabolic disorders. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT03528031.

Respiratory stress in mitochondrial electron transport chain complex mutants of Candida albicans activates Snf1 kinase response.

We have previously established that mitochondrial Complex I (CI) mutants of Candida albicans display reduced oxygen consumption, decreased ATP production, and increased reactive oxidant species (ROS) during cell growth. Using the Seahorse XF96 analyzer, the energetic phenotypes of Electron Transport Chain (ETC) complex mutants are further characterized in the current study. The underlying regulation of energetic changes in these mutants is determined in glucose and non-glucose conditions when compared to wild type (WT) cells. In parental cells, the rate of oxygen consumption remains constant for 2.5 h following the addition of glucose, oligomycin, and 2-DG, but glycolysis is highly active upon the addition of glucose. In comparison, over the same time period, electron transport complex mutants (CI, CIII and CIV) have heightened activities in both oxygen consumption and glycolysis upon glucose uptake. We refer to the response in these mutants as an "explosive respiration," which we believe is caused by low energy levels and increased production of reactive oxygen species (ROS). Accompanying this phenotype in mutants is a hyperphosphorylation of Snf1p which in Saccharomyces cerevisiae serves as an energetic stress response protein kinase for maintaining energy homeostasis. Compared to wild type cells, a 2.9- to 4.4-fold hyperphosphorylation of Snf1p is observed in all ETC mutants in the presence of glucose. However, the explosive respiration and hyperphosphorylation of Snf1 can be partially reduced by the replacement of glucose with either glycerol or oleic acid in a mutant-specific manner. Furthermore, Inhibitors of glutathione synthesis (BSO) or anti-oxidants (mito-TEMPO) likewise confirmed an increase of Sfn1 phosphorylation in WT or mutant due to increased levels of ROS. Our data establish the role of the C. albicans Snf1 as a surveyor of cell energy and ROS levels. We interpret the "explosive respiration" as a failed attempt by ETC mutants to restore energy and ROS homeostasis via Snf1 activation. An inherently high OCR baseline in WT C. albicans with a background level of Snf1 activation is a prerequisite for success in quickly fermenting glucose.