Triglyceride | EPFL Graph Search

A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from tri- and glyceride). Triglycerides are the main constituents of body fat in humans and other vertebrates, as well as vegetable fat. They are also present in the blood to enable the bidirectional transference of adipose fat and blood glucose from the liver, and are a major component of human skin oils. Many types of triglycerides exist. One specific classification focuses on saturated and unsaturated types. Saturated fats have no C=C groups; unsaturated fats feature one or more C=C groups. Unsaturated fats tend to have a lower melting point than saturated analogues; as a result, they are often liquid at room temperature. Chemical structure The three fatty acids substituents can be the same, but they are usually different. Many triglycerides are known because many fatty acids are known and their combinations are even more numerous. The chain le

Novel Molecular Probes for Non-invasive Optical Imaging of Fatty Acid and Triglyceride Uptake in Living Animals

Grigory Karateev

Molecular imaging allows noninvasive visualization of biological processes in their native environment within living systems. It can give a better understanding of fundamental biology, help in identifying disease mechanisms and visualizing pathological tissues, and enable monitoring disease progression and studying the drug efficacy in intact living organisms. Among various imaging modalities, bioluminescence and fluorescence imaging are powerful techniques that have become essential methods for non-invasive real-time studies of biological processes in vivo. The aim of my thesis was the development of novel fluorescent and bioluminescent probes for in vivo imaging of fatty acid and triglyceride uptake. The goal of my first project was the development of a near infrared fluorescent fatty acid probe for glioma imaging. Some tumors such as glioma may rely on the uptake of extracellular fatty acids. Fatty acids can therefore be considered as targeting molecules for these tumors and could be used to develop tumor-imaging probes. The probe design is based on a near-infrared fluorophore indocyanine green (ICG) that is conjugated to a long-chain fatty acid palmitic acid. The conjugation of ICG to a fatty acid (ICG-FA) was envisioned to improve cell permeability of the fluorophore and its accumulation in glioma. The ICG-FA probe was first evaluated for its ability to mimic the uptake of natural fatty acids in cells and was then applied for glioma imaging studies in vivo, where it showed significant tumor accumulation. As a proof-of-concept, the probe was tested for intraoperative image-guided surgery in a canine patent with mastocytoma, where it allowed intraoperative fluorescence tumor imaging and provided optical guidance for a surgeon during tumor resection. The aim of my second project was the development of bioluminescent triglyceride probes for real-time non-invasive imaging of triglyceride uptake in vivo. Applying an optimized stategy for generating conjugates with luciferin, I developed several bioluminescent triglyceride probes. These imaging tools were validated in cells and mice and were shown to mimic the absorption of natural triglycerides. The developed probes enabled sensitive non-invasive real-time imaging and quantification of triglyceride absorption in living mice. Futhermore, these probes were successfully used to demonstrate the effects of the anti-obesity drug orlistat and the influence of the gut microbiota on the intestinal absorption of triglycerides in vivo. Considering the high importance of triglycerides for human health and nutrition and their implication in several pathologies such as obesity, metabolic syndrome, type 2 diabetes and cancer, the bioluminescent triglyceride probes could offer valuable imaging tools for preclinical research.

EPFL2019

Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c

Johan Auwerx, Li Wang

We explored the effects of bile acids on triglyceride (TG) homeostasis using a combination of molecular, cellular, and animal models. Cholic acid (CA) prevents hepatic TG accumulation, VLDL secretion, and elevated serum TG in mouse models of hypertriglyceridemia. At the molecular level, CA decreases hepatic expression of SREBP-1c and its lipogenic target genes. Through the use of mouse mutants for the short heterodimer partner (SHP) and liver X receptor (LXR) alpha and beta, we demonstrate the critical dependence of the reduction of SREBP-1c expression by either natural or synthetic farnesoid X receptor (FXR) agonists on both SHP and LXR alpha and LXR beta. These results suggest that strategies aimed at increasing FXR activity and the repressive effects of SHP should be explored to correct hypertriglyceridemia.

2004

Hepatotoxicity induced by neonatal exposure to diethylstilbestrol is maintained throughout adulthood via the nuclear receptor SHP

Kristina Schoonjans

Background: Liver physiology is sensitive to estrogens, which suggests that the liver might be a target of estrogenic endocrine disrupters (EED). However, the long-term consequences of neonatal exposure to EED on liver physiology have rarely been studied. The nuclear receptor small heterodimer partner (SHP) mediates the deleterious effects of neonatal exposure to diethylstilbestrol (DES) on male fertility. Objectives: As SHP is involved in liver homeostasis, we aimed to determine whether neonatal estrogenic exposure also affected adult liver physiology through SHP. Male mouse pups were exposed to DES in the first 5 days of life. Results: DES exposure leads to alterations in the postnatal bile acid (BA) synthesis pathway. Neonatal DES-exposure affected adult liver BA metabolism and subsequently triglyceride (TG) homeostasis. The wild-type males neonatally exposed to DES exhibited increased liver weight and altered liver histology in the adult age. The use of deficient male mice revealed that SHP mediates the deleterious effects of DES treatment. These long-term effects of DES were associated with differently timed alterations in the expression of epigenetic factors. Conclusions: However, the molecular mechanisms by which neonatal exposure persist to affect the adult liver physiology remain to be defined. In conclusion, we demonstrate that neonatal DES exposure alters adult hepatic physiology in an SHP-dependent manner.

Informa Healthcare2014

Novel Molecular Probes for Non-invasive Optical Imaging of Fatty Acid and Triglyceride Uptake in Living Animals

Grigory Karateev

EPFL2019