S100A16, a novel lipogenesis promoting factor in livers of mice and hepatocytes in vitro

Abstract

To investigate the role of S100 calcium-binding protein A16 (S100A16) in hepatic lipid metabolism, S100a16 transgenic, S100a16 knockdown, and wildtype C57BL/6 mice were fed either a high-fat diet (HFD) or normal-fat diet (NFD) for 16 weeks. The results showed that for HFD-fed mice, S100a16 transgenic mice showed significantly more severe fatty liver than other HFD-fed mice, with a significant increase in serum triglyceride (TG) concentration, with more and larger lipid droplets in the liver, whereas S100a16 knockdown mice were completely opposite, with liver fat lesions and TG serological changes being the mildest; for NFD-fed mice, liver fat accumulation and serum TG concentrations were significantly lower than those fed HFD, and no significant lipid droplets were found in the liver. Further, we found that calmodulin (CaM) interacts with S100A16, a member of the AMP-activated protein kinase (AMPK) pathway. Our research found that S100A16 regulates the AMPK pathway-associated protein by interacting with CaM to regulate liver lipid synthesis. S100A16 regulates liver lipid metabolism through the CaM/CAMKK2/AMPK pathway. Overexpression of S100A16 promotes the deterioration of fatty liver induced by HFD, and low expression of S100A16 can attenuate fatty liver. K E Y W O R D Scalmodulin, fatty liver, S100 calcium-binding protein A16

Expressional and Prognostic Value of S100A16 in Pancreatic Cancer Via Integrated Bioinformatics Analyses

“…In our study, KEGG analysis showed that DEGs were concentrated mainly in the pathway related to pancreatic secretory function. Relevant studies have shown that S100A16 can reduce the sensitivity of 3T3-L1 to insulin, overexpression of S100A16 can promote lipid synthesis of 3T3-L1 preadipocytes, inhibiting glucose uptake under insulin stimulation, and cause insulin resistance (Kan et al, 2019). Overexpression of S100A16 in 3T3-L1 cells promotes proliferation and differentiation of 3T3-L1 cells, which is consistent with our findings.…”

S100 Proteins in Fatty Liver Disease and Hepatocellular Carcinoma

“…However, for most of the S100 members, their impact on Ca 2+ signaling and Ca 2+ -dependent cellular processes remains poorly characterized and needs further investigations. Currently, recent studies support a wide spectrum of essential and non-redundant cellular actions for S100 proteins [ 36 , 77 ], as well illustrated by the lethality of single S100 gene knockout such as S100A8 [ 79 ] or S100A16 [ 80 ] in mice.…”

Interaction of calcium binding protein S100A16 with myosin-9 promotes cytoskeleton reorganization in renal tubulointerstitial fibrosis

“…Male C57BL/6J (WT) mice, heterozygous S100A16 knockout (S100A16 +/− ) mice, and S100A16 transgenic (S100A16 Tg ) mice (n = 16 each group) weighing approximately 20-24 g were acquired from the Animal Center of Nanjing Medical University. All protocols for animal experimentation and maintenance adhered to the guidelines of the Institutional Animal Care and Use Committee at Nanjing Medical University 12,13,18 . S100A16 Tg mice were engineered to overexpress S100A16 under the control of the PCAG promoter.…”

“…These proteins S100A16, a newly discovered member of the S100 family, is widely expressed in various human tissues and organs 9,10 , and its overexpression has been linked to increased adipocyte proliferation and lipogenesis 11,12 . S100A16 also appears to participate in glucose metabolism disorders 9,13 , but its full physiological and pathogenic function remains unclear. S100 proteins including S100A16 contain Ca 2+ -binding EF-hand motifs (helix-loop-helix structural domain) to interact with calcium for its biological function 14 .…”