title: Fatty Acid β-Oxidation Plays a Key Role in Regulating cis-Palmitoleic Acid Levels in the Liver.
abstract: Different monounsaturated fatty acid (MUFA) species have distinct pathophysiological activities. cis-Palmitoleic acid (16:1n-7) was previously reported to improve insulin sensitivity in animal studies. The proportions of hepatic MUFAs are generally considered to reflect changes in the activities of fatty acid modifications (∆9 desaturation and fatty acid elongation). However, hepatic levels of 16:1n-7 are markedly lower than those of oleic acid (18:1n-9). Nevertheless, no convincing explanation has yet been provided for the low level of 16:1n-7. We hypothesized that fatty acid degradation plays a key role in maintaining a low 16:1n-7 proportion in the liver. In order to corroborate the link between β-oxidation and the proportion of 16:1n-7, rats were fed a control diet, fed a fat-free diet to up-regulate fatty acid modifications, but not β-oxidation, or treated with clofibric acid to up-regulate fatty acid modifications and β-oxidation. The nutritional manipulation markedly increased the proportions of 16:1n-7, 18:1n-9, and cis-vaccenic acid (18:1n-7). Although the pharmacological manipulation enhanced fatty acid modifications to largely the same extent as the nutritional manipulation and markedly elevated the proportion of 18:1n-9, those of 16:1n-7 and 18:1n-7 remained largely unchanged. The oxidation rates of 16:1n-7, 18:1n-9, and 18:1n-7 in liver slices were in the following order: 16:1n-7>18:1n-7≑18:1n-9 in control livers, and were increased by the pharmacological manipulation and decreased by the nutritional manipulation. These results strongly suggest that β-oxidation, in concert with fatty acid modifications, plays a key role in regulating the MUFA profile and is crucially involved in maintaining low 16:1n-7 levels in the liver.
authors.affiliation: School of Pharmaceutical Sciences, Josai University.
authors.forename: Kohei
authors.initials: K
authors.lastname: Kawabata
authors.forename: Minako
authors.initials: M
authors.lastname: Karahashi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Yukiho
authors.initials: Y
authors.lastname: Tsuji
authors.forename: Tohru
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Mari
authors.initials: M
authors.lastname: Okazaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mitsumoto
authors.forename: Naomi
authors.initials: N
authors.lastname: Kudo
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kawashima
mesh_terms: D000818:Animals; D064429:Fatty Acid Synthases / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D017208:Rats, Wistar; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism; D000217:Acyltransferases
chemical_list: D064429:Fatty Acid Synthases; D005227:Fatty Acids; D008049:Lipase; D013230:Stearoyl-CoA Desaturase; C571275:PNPLA2 protein, rat; D000217:Acyltransferases