Hepatic ∆6-desaturase activity in lean and genetically obese ob/ob mice

Abstract

Hepatic delta 6-desaturase activity is primarily located in the mitochondrial fraction in mice. Both delta 6- and delta 5-desaturase activities are increased in the liver of young (6-week-old) obese mice. The increase in hepatic delta 6-desaturase activity in obese mice does not occur until weaning. Neither restriction of food intake nor hyperinsulinaemia normalize hepatic delta 6-desaturase activity of obese mice. Both cold acclimation and tri-iodothyronine (30 micrograms/day per kg) decreased hepatic delta 6-desaturase activity of obese mice to levels observed in lean mice, whereas the increase in activity in obese mice was still maintained after the induction of hypothyroidism.

The fatty acid desaturase 2 (FADS2) gene product catalyzes Δ4 desaturation to yield n-3 docosahexaenoic acid and n-6 docosapentaenoic acid in human cells

“…This observed shorter product may be due to protein degradation or cleavage. FADS2 is known to code for ER proteins; however, mitochondrial Δ6‐desaturase ( FADS2 ) activity has been reported more than once (7, 60).…”

“…This observed shorter product may be due to protein degradation or cleavage. FADS2 is known to code for ER proteins; however, mitochondrial D6-desaturase (FADS2) activity has been reported more than once (7,60). The D6-desaturase activity was 2-fold higher in a mouse liver mitochondrial fraction compared to the microsomal fraction (7).…”

“…Humans can consume 22:6n‐3 and 22:5n‐6 from marine foods and can also biosynthesize them from the corresponding precursor fatty acids 18:3n‐3 and 18:2n‐6 and downstream intermediates by sequential desaturations and elongations (5). The desaturase biosynthetic activities are known to localize to the endoplasmic reticulum (ER) (6), though over the years data suggest that they operate in other organelles, chiefly the mitochondria (7) and nuclear membrane (8). The synthesis of 22:6n‐3 is widely accepted to be limited in humans (9), with serious translational consequences.…”

A novel FADS1 isoform potentiates FADS2-mediated production of eicosanoid precursor fatty acids

“…In mammals, several highly conserved hexamer sequence variants exist upstream of the polyadenylation sites ( 44 ), which mediate termination of transcription followed by polyadenylation ( 45 ). In our study, two amplicons (1,114 bp, and 1,156 bp) had a CATAAA poly(A) signal 11 bp upstream of the polyadenylation start site; one amplicon (1,460 bp) had a ACTAAA poly(A) signal 124 bp upstream of the polyadenylation start site; no proper poly(A) signal could be identifi ed for two amplicons (1,606 bp and 1,620 bp); and two amplicons (2,603 bp and 3,750 bp) had requiring FADS2 has been appeared periodically ( 33,53 ), and desaturation has been reported in nuclei ( 54 ). Here we show for the fi rst time molecular evidence that FADS1CS is localized to the mitochondria by live cell imaging and subcellular fractionation using a GFP tagging system and immunoblotting.…”

Design, synthesis, and in vivo activity of novel inhibitors of delta-5 desaturase for the treatment of metabolic syndrome

“…1-3 A correlation has been observed between the level of activity of desaturases and various disease states, including obesity. 4,5 For instance, regulation of both delta-5 desaturase [also known as fatty acid desaturase (FADS1)] and delta-6 desaturase activity has been associated with changes in body weight in mice, humans and other animals. Desaturases are a family of enzymes that are involved in the production of poly-unsaturated fatty acids, beginning with the desaturation of palmitic acid, and are named according to the type of fatty acid they generate (delta-5, delta-6, and delta-9 desaturase).…”