title: Linoleic acid and stearic acid elicit opposite effects on AgRP expression and secretion via TLR4-dependent signaling pathways in immortalized hypothalamic N38 cells.
abstract: The regulation of food intake is a promising way to combat obesity. It has been implicated that various fatty acids exert different effects on food intake and body weight. However, the underlying mechanism remains poorly understood. The aim of the present study was to investigate the effects of linoleic acid (LA) and stearic acid (SA) on agouti-related protein (AgRP) expression and secretion in immortalized mouse hypothalamic N38 cells and to explore the likely underlying mechanisms. Our results demonstrated that LA inhibited, while SA stimulated AgRP expression and secretion of N38 cells in a dose-dependent manner. In addition, LA suppressed the protein expression of toll-like receptor 4 (TLR4), phosphorylation levels of JNK and IKKα/β, suggesting the inhibition of TLR4-dependent inflammation pathway. However, the above mentioned inhibitory effects of LA were eliminated by TLR4 agonist lipopolysaccharide (LPS). In contrast, SA promoted TLR4 protein expression and activated TLR4-dependent inflammation pathway, with elevated ratio of p-JNK/JNK. While TLR4 siRNA reversed the stimulatory effects of SA on AgRP expression and TLR4-dependent inflammation. Moreover, we found that TLR4 was also involved in LA-enhanced and SA-impaired leptin/insulin signal pathways in N38 cells. In conclusion, our findings indicated that LA elicited inhibitory while SA exerted stimulatory effects on AgRP expression and secretion via TLR4-dependent inflammation and leptin/insulin pathways in N38 cells. These data provided a better understanding of the mechanism underlying fatty acids-regulated food intake and suggested the potential role of long-chain unsaturated fatty acids such as LA in reducing food intake and treating obesity.
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou 510642, PR China.
authors.forename: Songbo
authors.initials: S
authors.lastname: Wang
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou 510642, PR China.
authors.forename: Nana
authors.initials: N
authors.lastname: Xiang
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou 510642, PR China.
authors.forename: Liusong
authors.initials: L
authors.lastname: Yang
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou 510642, PR China.
authors.forename: Canjun
authors.initials: C
authors.lastname: Zhu
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou 510642, PR China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou 510642, PR China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou 510642, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gao
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou 510642, PR China.
authors.forename: Qianyun
authors.initials: Q
authors.lastname: Xi
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou 510642, PR China.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou 510642, PR China. Electronic address: shugang@scau.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Shu
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and ALLTECH-SCAU Animal Nutrition Control Research Alliance, South China Agricultural University, Guangzhou 510642, PR China. Electronic address: qyjiang@scau.edu.cn.
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Jiang
mesh_terms: D054369:Agouti-Related Protein / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000818:Animals; D004435:Eating / Q000187:drug effects*; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D019787:Linoleic Acid / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D013229:Stearic Acids / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D020738:Leptin; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D013229:Stearic Acids; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C031183:stearic acid; D019787:Linoleic Acid; D051550:I-kappa B Kinase
keywords: AgRP; Linolenic acid; N38 cells; Obesity; Stearic acid; TLR4