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Palmitate-Induced Suppression of IGF binding protein-3 Leads to Liver Inflammation

Feb 6, 2017 8:16:08 AM / by Stacy Matthews Branch, DVM, PhD

Research was conducted to better understand the link between IGFBP-3 and NASH by measuring macrophages derived from monocytes and treated with palmitate.Insulin-like growth factors (IGFs) are hormones resembling insulin and are important for normal cell growth and division. IGF-binding proteins (IGFBPs) regulate IGF action leading to changes in their effects in the body. IGF-binding protein-3 (IGFBP-3) is the most abundant of the IGFBPs and is made primarily in kupffer cells (specialized liver macrophages).

IGFBP-3 has anti-inflammatory and antitumor activity and exists at lower levels in those with obesity, a risk factor for the development of nonalcoholic fatty liver disease (NAFLD). NAFLD is a public health issue affecting about 30% of the population of western civilizations and can progress to liver cirrhosis and cancer. Also interesting is that liver toxicity due to increased blood levels of saturated fatty acids, such as palmitate, plays an important role in the inflammation seen in nonalcoholic steatohepatitis (NASH, a more serious form of NAFLD).

Research was conducted to better understand the link between IGFBP-3 and NAFLD or NASH, and to determine if palmitate can affect the production and secretion of IGFBP-3 and inflammatory cytokines. The studies involved measuring IGFBP-3, as well as IL-8 and other inflammatory cytokines, in the blood and tissues of patients with or without NAFLD or NASH. The cytokines were also measured in macrophages derived from monocytes obtained from HemaCare and treated with palmitate. Cytokines were also measured in liver cancer and monocyte cell lines treated with palmitate.

Patients with NAFL and NASH had decreased IGFBP-3 and increased IL-8 blood levels. IL-8 levels were much higher in liver tissue from those with NAPLD or NASH compared to nonaffected people with or without obesity. When palmitate was incubated with a cancer cell line, levels of lL-8 expression increased. It was also found that palmitate inhibited the secretion of IGFBP-3 in the monocyte cell line.

The study results show how reduced IGFBP-3 levels in NAFLD/NASH are linked to increased IL-8 levels. Palmitate can inhibit IGFBP-3, keeping IGFBP-3 from preventing IL-8 production by the liver. This new knowledge regarding IGFBP-3 can lead to further studies that could ultimately help in the development of IGFBP-3-based treatments for NASH and for the prevention of associated cancer development.

If you’re interested in using monocyte cells for your research, visit us online or call at 877-397-3087 today.

Reference:
Min, H.-K. et al. "Suppression Of IGF Binding Protein-3 By Palmitate Promotes Hepatic Inflammatory Responses". The FASEB Journal. N.p., 2017. Web. 26 Jan. 2017.

Topics: Inflammation, Macrophages, Monocytes, stem cell research, Basic Research

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