title: Serum amyloid A1 levels and amyloid deposition following a high-fat diet challenge in transgenic mice overexpressing hepatic serum amyloid A1.
abstract: Serum amyloid A (SAA) is an acute-phase response protein in the liver, and SAA1 is the major precursor protein involved in amyloid A amyloidosis. This amyloidosis has been reported as a complication in chronic inflammatory conditions such as arthritis, lupus, and Crohn's disease. Obesity is also associated with chronic, low-grade inflammation and sustained, elevated levels of SAA1. However, the contribution of elevated circulating SAA1 to metabolic disturbances and their complications is unclear. Furthermore, in several recent studies of transgenic (TG) mice overexpressing SAA1 that were fed a high-fat diet (HFD) for a relatively short period, no relationship was found between SAA1 up-regulation and metabolic disturbances. Therefore, we generated TG mice overexpressing SAA1 in the liver, challenged these mice with an HFD, and investigated the influence of elevated SAA1 levels. Sustained, elevated levels of SAA1 were correlated with metabolic parameters and local cytokine expression in the liver following 16 weeks on the HFD. Moreover, prolonged consumption (52 weeks) of the HFD was associated with impaired glucose tolerance and elevated SAA1 levels and resulted in systemic SAA1-derived amyloid deposition in the kidney, liver, and spleen of TG mice. Thus, we concluded that elevated SAA1 levels under long-term HFD exposure result in extensive SAA1-derived amyloid deposits, which may contribute to the complications associated with HFD-induced obesity and metabolic disorders.
authors.affiliation: a School of Life Sciences, KNU Creative BioResearch Group (BK21 Plus Project), Kyungpook National University, 1370 Sankyuk-dong, Daegu, 702-701, Republic of Korea.
authors.forename: Woo Young
authors.initials: WY
authors.lastname: Jang
authors.affiliation: a School of Life Sciences, KNU Creative BioResearch Group (BK21 Plus Project), Kyungpook National University, 1370 Sankyuk-dong, Daegu, 702-701, Republic of Korea.
authors.forename: Jain
authors.initials: J
authors.lastname: Jeong
authors.affiliation: a School of Life Sciences, KNU Creative BioResearch Group (BK21 Plus Project), Kyungpook National University, 1370 Sankyuk-dong, Daegu, 702-701, Republic of Korea.|b Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Dong-gu, Daegu, 701-310 Republic of Korea.
authors.forename: Seonggon
authors.initials: S
authors.lastname: Kim
authors.affiliation: a School of Life Sciences, KNU Creative BioResearch Group (BK21 Plus Project), Kyungpook National University, 1370 Sankyuk-dong, Daegu, 702-701, Republic of Korea.
authors.forename: Min-Cheol
authors.initials: MC
authors.lastname: Kang
authors.affiliation: a School of Life Sciences, KNU Creative BioResearch Group (BK21 Plus Project), Kyungpook National University, 1370 Sankyuk-dong, Daegu, 702-701, Republic of Korea.
authors.forename: Yong Hun
authors.initials: YH
authors.lastname: Sung
authors.affiliation: a School of Life Sciences, KNU Creative BioResearch Group (BK21 Plus Project), Kyungpook National University, 1370 Sankyuk-dong, Daegu, 702-701, Republic of Korea.
authors.forename: Minjee
authors.initials: M
authors.lastname: Choi
authors.affiliation: a School of Life Sciences, KNU Creative BioResearch Group (BK21 Plus Project), Kyungpook National University, 1370 Sankyuk-dong, Daegu, 702-701, Republic of Korea.
authors.forename: Si Jun
authors.initials: SJ
authors.lastname: Park
authors.affiliation: c Department of Animal Science, Kyungpook National University, 386 Gajangdong, Sangju, 742-711, Republic of Korea.
authors.forename: Myoung Ok
authors.initials: MO
authors.lastname: Kim
authors.affiliation: a School of Life Sciences, KNU Creative BioResearch Group (BK21 Plus Project), Kyungpook National University, 1370 Sankyuk-dong, Daegu, 702-701, Republic of Korea.
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: a School of Life Sciences, KNU Creative BioResearch Group (BK21 Plus Project), Kyungpook National University, 1370 Sankyuk-dong, Daegu, 702-701, Republic of Korea.
authors.forename: Zae Young
authors.initials: ZY
authors.lastname: Ryoo
mesh_terms: D000210:Acute-Phase Reaction; D000686:Amyloidosis / Q000097:blood / Q000150:complications; D000818:Animals; D001168:Arthritis / Q000097:blood / Q000150:complications; D001786:Blood Glucose / Q000378:metabolism; D003424:Crohn Disease / Q000097:blood / Q000150:complications; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005260:Female; D007328:Insulin / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008822:Mice, Transgenic; D009765:Obesity / Q000097:blood / Q000150:complications; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; D007328:Insulin; D053583:Interleukin-1beta; D015850:Interleukin-6; C489995:Saa2 protein, mouse; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha
keywords: amyloidosis; amylose; high-fat diet; inflammation; metabolic complication; obesity; obésité; régime riche en gras; serum amyloid A; sérum amyloïde A; trouble métabolique