Associations between high-metabolic rate organ masses and fasting hunger: a study using whole-body magnetic resonance imaging in healthy males

Background: Fat-free mass (FFM) has been shown to be positively associated with hunger and energy intake, an association mediated by resting metabolic rate (RMR). However, FFM comprises a heterogeneous group of tissues with distinct metabolic rates, and it remains unknown how specific high-metabolic rate organs contribute to the degree of perceived hunger. Objective: To examine whether FFM and its anatomical components were associated with fasting hunger when assessed at the tissue-organ level. Design: Body composition (quantitative magnetic resonance and magnetic resonance imaging), RMR and whole-body glucose oxidation (indirect calorimetry), HOMA-index as a marker of insulin sensitivity, nitrogen balance and fasting hunger (visual analogue scales) were assessed in 21 healthy males (age = 25 ± 3y; BMI = 23.4 ± 2.1 kg/m2) after 3 days of controlled energy balance. Results: FFM (rs = 0.39; p = 0.09), RMR (rs = 0.52; p = 0.02) and skeletal muscle mass (rs = 0.57; p = 0.04), but not fat mass (rs = −0.01; p = 0.99), were positively associated with fasting hunger. The association between the combined mass of high-metabolic rate organs (i.e., brain, liver, kidneys and heart; rs = 0.58; p = 0.006) and fasting hunger was stronger than with FFM as a uniform body component. The strongest individual association was between liver mass and fasting hunger (rs = 0.51; p = 0.02). No associations were observed between glucose parameters, markers of insulin sensitivity and fasting hunger. The encephalic measure, an index of brain-to-body energy allocation, was negatively associated with fasting hunger (rs = −0.51; p = 0.02). Conclusions: Fasting hunger was more strongly associated with the combined mass of high-metabolic rate organs than with FFM as a uniform body component, highlighting the importance of integrating individual tissue-organ masses and their functional correlates into homeostatic models of human appetite. The association between liver mass and fasting hunger may reflect its role in ensuring the brain's basal energy needs are met

Isocitrate Dehydrogenase Is Important for Nitrosative Stress Resistance in Cryptococcus neoformans, but Oxidative Stress Resistance Is Not Dependent on Glucose-6-Phosphate Dehydrogenase▿

The opportunistic intracellular fungal pathogen Cryptococcus neoformans depends on many antioxidant and denitrosylating proteins and pathways for virulence in the immunocompromised host. These include the glutathione and thioredoxin pathways, thiol peroxidase, cytochrome c peroxidase, and flavohemoglobin denitrosylase. All of these ultimately depend on NADPH for either catalytic activity or maintenance of a reduced, functional form. The need for NADPH during oxidative stress is well established in many systems, but a role in resistance to nitrosative stress has not been as well characterized. In this study we investigated the roles of two sources of NADPH, glucose-6-phosphate dehydrogenase (Zwf1) and NADP+-dependent isocitrate dehydrogenase (Idp1), in production of NADPH and resistance to oxidative and nitrosative stress. Deletion of ZWF1 in C. neoformans did not result in an oxidative stress sensitivity phenotype or changes in the amount of NADPH produced during oxidative stress compared to those for the wild type. Deletion of IDP1 resulted in greater sensitivity to nitrosative stress than to oxidative stress. The amount of NADPH increased 2-fold over that in the wild type during nitrosative stress, and yet the idp1Δ strain accumulated more mitochondrial damage than the wild type during nitrosative stress. This is the first report of the importance of Idp1 and NADPH for nitrosative stress resistance