Presentation_1_Nutritional Ketosis Increases NAD+/NADH Ratio in Healthy Human Brain: An in Vivo Study by 31P-MRS.PDF

<p>Ketones represent an important alternative fuel for the brain under glucose hypo-metabolic conditions induced by neurological diseases or aging, however their metabolic consequences in healthy brain remain unclear. Here we report that ketones can increase the redox NAD⁺/NADH ratio in the resting brain of healthy young adults. As NAD is an important energetic and signaling metabolic modulator, these results provide mechanistic clues on how nutritional ketosis might contribute to the preservation of brain health.</p

Bar plots describing metabolite variations in the study population stratified in four quartiles according to visceral fat adiposity (intraperitoneal fat) at V2.

<p>Statistical significance is reported in Table S3. Key: PC-O, 1-O-alkyl-2- acylglycerophosphocholines. Assignment of PC-O species is made on the assumption that only even numbered carbon chains are present. A potential overlap between PC species containing odd-chain fatty acids and even-chained PC-O species cannot be excluded with low mass resolution.</p

Statistically significant Spearman correlation map between body fat composition parameters and clinical measures (95% confidence interval).

<p>Log₁₀ values of IPVF, VAT/SAT, VAT/total abdominal fat were strongly associated with HOMA-IR (r = 0.39, p = 0.015; r = 0.56, p<0.001; r = 0.55, p<0.001) and fasting insulin (r = 0.35, p = 0.0275; r = 0.49, p = 0.0017; r = 0.48, p = 0.0020). Strong associations were observed with ALAT (r = 0.39, p = 0.0128; r = 0.37, p = 0.0175; r = 0.38, p = 0.0167) and ALAT/ASAT ratio (r = 0.44, p = 0.0044; r = 0.35, p = 0.0268; r = 0.35, p = 0.0302). IPVF and Log₁₀ values of IPVF correlated with waist (r = 0.55, p<0.001; r = 0.35, p = 0.04) and waist/hip ratio (r = 0.69, p<0.001; r = 0.52, p = 0.0017), but not Log₁₀ values of VAT/SAT and VAT/total abdominal fat. NB: Blue denotes negative correlation, orange denotes positive correlation, and black denotes no correlation.</p

Plot describing metabolite importance and robustness in predicting visceral fat adiposity as assessed by Random forest analysis using metabolic data collected at V0 and V2.

<p>Visceral adiposity was associated with increasing concentrations of amino acids (glutamine, leucine/isoleucine, phenylalanine and tyrosine), lysophosphatidylcholine LPC 24∶0 and diacyl phospholipids (PC 30∶0, PC 34∶4). In addition, visceral adiposity was marked by a depletion in ether lipid species PC<i>-O</i> 36∶3, PC<i>-O</i> 40∶3, PC<i>-O</i> 40∶4, PC<i>-O</i> 40∶6, PC<i>-O</i> 42∶2, PC<i>-O</i> 42∶3, PC<i>-O</i> 42∶4, PC<i>-O</i> 44∶3, PC<i>-O</i> 44∶4, PC<i>-O</i> 44∶6, and two diacyl phosphocholines (PC 42∶0 and PC 42∶2). To reflect the weight of the selected biomarkers in the classification of visceral adiposity, a pooled mean decrease of accuracy for each compound was calculated from 10000 forest generations. Higher variable importance corresponds to higher values of pooled mean decrease in accuracy. Key: IPVF, intraperitoneal fat volume; LPC, Lysophosphatidylcholines; PC, Phosphatidylcholines; PC-O, 1-O-alkyl-2- acylglycerophosphocholines; Ratio1, intraperitoneal/subcutaneous fat ratio; Ratio 2, intraperitoneal/abdominal fat ratio. Assignment of PC-O species is made on the assumption that only even numbered carbon chains are present. A potential overlap between PC species containing odd-chain fatty acids and even-chained PC-O species cannot be excluded with low mass resolution.</p

Metabolite variations across subjects stratified according to intraperitoneal/abdominal fat ratio.

<p>NB: Blood plasma metabolites highlighted by multivariate analyses are reported as mean values ± SD. Key: Qi: data for population quartile i according to intraperitoneal/abdominal fat ratio. 12-HETE, 12-hydroxy-eicosatetraenoic acid; 15-HETE, 12-hydroxy-eicosatetraenoic acid; 9-HODE, 9-Hydroxy-10,12-octadecadienoic acid; AA, arachidonic acid; LPC, Lysophosphatidylcholines; PC, Phosphatidylcholines; PC-O, 1-O-alkyl-2- acylglycerophosphocholines; SM, Sphingomyelines; SM-OH, Hydroxy-Sphingomyelin.</p>*<p>Assignment of PC-O species is made on the assumption that only even numbered carbon chains are present. A potential overlap between PC species containing odd-chain fatty acids and even-chained PC-O species cannot be excluded with low mass resolution.</p

Descriptive statistics of subjects stratified according to intraperitoneal/abdominal fat ratio.

<p>Key: Qi: data for population quartile i according to intraperitoneal/abdominal fat ratio. BMI = body mass index, HDL-C =  high density lipoprotein cholesterol, homeostasis model assessment of insulin resistance =  HOMA-IR, LDL-C =  low density lipoprotein cholesterol, TG =  triglycerides, MAP =  mean arterial blood pressure, ALAT =  alanine aminotransferase, ASAT =  aspartate aminotransferase, GGT =  gamma-glutamyl transpeptidase, NEFAs = non esterified fatty acids. Data are reported as mean values ± SD.</p

Insulin and glucose response to oral glucose tolerance test according to intraperitoneal/abdominal fat ratio.

<p>NB: Values are reported as mean values ± SD. Key: Qi: data for population quartile i according to intraperitoneal/abdominal fat ratio.</p