engleski

Liver lipogenesis in diabetes and metabolic syndrome: benefits and limitations of animal models

Whole body fatty acids can originate from three different sources: food, de novo lipogenesis and bioconversion. Fatty acids generated de novo, as well as fatty acids derived from the food can be bioconverted to longer-chain fatty acids with more carbon atoms and/or double bonds, by a series of steps of desaturation and elongation, or shortened by β-oxidation steps and recycled between peroxisomes and the endoplasmatic reticulum. Regulation of these steps involves desaturases (Δ9D, Δ6D, Δ5D) and elongases (Elovl2, Elovl5 and Elovl6) as well as different metabolites (glucose), hormones (insulin) and transcriptional factors (peroxisome proliferator-activated receptors α, PPARα ; sterol response element-binding protein-1c, SREBP-1c ; liver X receptor, LXR ; carbohydrate- regulatory element binding protein, ChREBP ; MAX-like factor X, MLX) and microRNA. Nutrition (substrate availability) and competition for rate-limiting enzymes for the desaturation as well as partitioning into oxidation could substantially contribute or even override other regulatory mechanisms. Metabolic diseases, such as diabetes, obesity or metabolic syndrome, are characterized with changes in lipogenesis in different tissues including liver, which is besides adipose tissue, the central organ for lipogenesis. Consequently, the fatty acid profile of liver changes, which could have profound influence on the fatty acid profile of other organs. The most important is brain, because brain’s long chain fatty acid profile depends on liver synthesis. The investigation of liver lipogenesis during metabolic disorders in animal models is challenging due to the highly complex regulation of liver lipogenesis as well as diversity in animal species and strains used. Additional challenge is diversity of nutritional and pharmacological interventions used to induce diabetes type 1 or 2 or metabolic syndrome.

lipogenesis ; rodents ; diabetes ; metabolic syndrome

nije evidentirano