Biology subjects

Lafourcade, C. A.

Publications and source records attributed to Lafourcade, C. A..

2 recordsLinked to original sources

bioRxiv2026

Intestinal fructose metabolism drives unsaturated fat absorption and synergizes with GLP-1 receptor agonism to promote weight loss

High-fat, high-sucrose (HFHS) diets are established risk factors for obesity. In the intestine, sucrose is hydrolyzed into glucose and fructose, with fructose being taken up by epithelial cells and phosphorylated by ketohexokinase (KHK). We hypothesized that KHK is required for the obesogenic effects of HFHS diets and performed genetic and pharmacologic experiments in mice using diet-induced obesity (DIO) models. We show that genetic loss of KHK prevents HFHS-induced weight gain and intestinal villus elongation. Moreover, pharmacologic inhibition of KHK (KHKi) promotes weight and fat loss during continued HFHS feeding in DIO mice and enhances weight loss and weight maintenance during and after incretin-mimetic therapy. The anti-obesogenic effects of KHKi were associated with delayed intestinal lipid absorption, reprogramming of lipid metabolism in the distal intestinal epithelium, and reduced absorption of unsaturated dietary fats. Together, these findings identify fructose metabolism as a key regulator of intestinal lipid handling and suggest that fructose promotes obesity, in part, by enhancing intestinal lipid absorption and metabolism.

cell biology↗

bioRxiv2020

The eNOS-dependent S-nitrosylation of the NF-κB subunit p65 has neuroprotective consequences in excitotoxicity

Cell death by glutamate excitotoxicity, mediated by N-methyl-D-aspartate (NMDA) receptors, negatively impacts brain function, including but not limited to hippocampal neurons. The NF-{kappa}B transcription factor (composed mainly of p65/p50 subunits) contributes to neuronal death in excitotoxicity, while its inhibition should improve cell survival. Using the biotin switch method, subcellular fractionation, immunofluorescence and luciferase reporter assays, we found that NMDA stimulated NF-{kappa}B activity selectively in hippocampal neurons, while endothelial nitric oxide synthase (eNOS), an enzyme expressed in neurons, is involved in the S-nitrosylation of p65 and consequent NF-{kappa}B inhibition in cerebrocortical, i.e., resistant neurons. The S-nitro proteomes of cortical and hippocampal neurons revealed that different biological processes are regulated by S-nitrosylation in susceptible and resistant neurons, bringing to light that protein S-nitrosylation is a ubiquitous post-translational modification, able to influence a variety of biological processes including the homeostatic inhibition of the NF-{kappa}B transcriptional activity in cortical neurons exposed to NMDA receptor overstimulation.

neuroscience↗