LBSUN152 The Warburg Effect And Complex Thermomics Inform Phenotypic Expression

Abstract

Abstract Introduction As technology reveals biological complexity, integration of vast clinical and multi-omic data utilizing artificial intelligence promises to clarify confusion. We have utilized challenge tests to inform algorithmic graphs recognizing heat as foundational for understanding phenotypic variation. Thermomics, describing complex thermic influences that are difficult to objectively quantify thereby compromising application to AI, are readily included in practice-derived models. Methods For the past 45 years cases have been evaluated with oral calcium challenge and immersion in water while observing changes in urinary composition. Between 2001 and 2010 respiratory gas exchange following a high carbohydrate meal combined with pulsatile insulin revealed metabolic variance that combined with basic, translational and clinical data of others informed generation of algorithmic graphs. COVID 19 served to clarify the effect of ACE2 disruption by predicting divergent phenotypic expression mediated by calciotropic hormones. Results Extraction of O2 from glucose, a consequence of fatty acid synthesis producing R/Q > 1 is modeled as foundational for metabolic evolution. This Warburg effect, recognized in proliferating malignant cells, was observed at the systemic level in humans and, modeled as mediated by hypoxia inducible factors regulating glucose uptake and suppression of beta-oxidation. Higher order orchestration is governed by a signaling structure including PTH, PTHrP, FGF23, Klotho, prolactin, growth hormone, IGFs, insulin, SGLT2, thyroid, adrenal and vit D while salt inducible kinase contributes to understanding of terrestrial adaptation. Inclusion of thermomics leads to prediction of a favorable effect of sub-cutaneous adipose beiging on CNS function mediated by circulating Klotho as a constraint on FGF23 in amelioration of Long COVID by phentermine that is also effective in hypophosphatasia where the exercise induced beiging, induced by irisin is known to be dependent upon alkaline phosphatase. The post-exertional malaise of Myalgic Encephalomyelitis, where exercise induces elevation in R/Q and reduced work capacity, has informed modeling of the systemic Warburg effect. The models are further validated with mechanistic explanation for recent reports of marked increases of R/Q in human Paget's disease and CEBPb expression dependence mimicking Alzheimer's and limiting life span in mice. Conclusions The value of practice is demonstrated by the ability to model thermomics even when difficult to quantify. The work is validated by explanation of old conundrums, discovery of treatment for unresolved problems, facilitation of case-based discovery and integration of emerging data from basic sciences. The Warburg effect when recognized as foundational to biology, contributes to a General Theory of Metabolism applicable to effective personalization of care. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.