Insulin‐like growth factor binding protein 7 accelerates hepatic steatosis and insulin resistance in non‐alcoholic fatty liver disease

Abstract

| INTRODUC TI ONNon-alcoholic fatty liver disease (NAFLD) is a complex, chronic metabolic disorder characterized by ectopic accumulation of triglycerides (TG) in the liver without a history of alcohol abuse. 1 NAFLD consists of simple steatosis and non-alcoholic steatohepatitis, which ultimately develop into severe cirrhosis and even hepatocellular carcinoma. Recently, the prevalence of NAFLD has increased rapidly and has reached 20%-30% in the urban population of China. 2The pathogenesis of NAFLD is mainly attributed to hepatic lipid accumulation and insulin resistance, since the liver plays a vital role in regulating lipid and glucose metabolism. 3 Insulin resistance resulting from lipid accumulation is referred to as a primary step in the progress of NAFLD due to its crucial role in maintaining the balance of glucose and hepatic TG homeostasis. In the liver, insulin resistance could accelerate NAFLD and lead to hyperinsulinaemia by enhancing the inflow of de novo lipogenesis (DNL). 4 Although various risk factors, such as inflammation, fatty acid synthesis and oxidative stress, have been demonstrated to be involved in NAFLD progression, the exact mechanism underlying NAFLD progression remains unclear. 5Insulin-like growth factor (IGF)-binding protein (IGFBP) 7, also known as mac25, IGFBP-related protein (IGFBP-rP), tumour adhesion factor (TAF) and angiomodulin (AGM), is a secreted, cysteinerich protein that belongs to the IGFBP superfamily. 6 IGFBP7 contains AbstractAn association between increased insulin-like growth factor binding protein-7 (IGFBP7) expression and insulin resistance in metabolic diseases has been reported.However, the role and molecular mechanism of IGFBP-7 in non-alcoholic fatty liver disease (NAFLD) remains largely unknown. Therefore, the potential function of R E FE R E N C E S

Determining the temporal, dose, and composition effects of nutritional substrates in an in vitro model of intrahepatocellular triglyceride accumulation

“…While primary human hepatocytes are considered a gold standard, the high costs, limited culturing capability, potential for low cell viability, and the variability between donors and batches makes it challenging to use them as a workhorse model. Immortalized cell lines (e.g., Huh7 and HepG2) are commonly used as a more accessible and robust model; however, previous studies (Gómez‐Lechón et al, 2007; Penke et al, 2017; Su et al, 2019; Yan et al, 2019) have cultured hepatocyte cell lines in supraphysiological concentrations of nutrients (between 100 and 2000 μM of only one or two FAs [palmitate, oleate, or a combination of both], alongside 5.5–25 mM of glucose), which may, in part, explain why they have poorly recapitulated primary hepatocytes.…”

Ursolic acid ameliorates adipose tissue insulin resistance in aged rats via activating the Akt‑glucose transporter 4 signaling pathway and inhibiting inflammation

“…During ageing, the body's metabolic changes are closely associated with several prevalent medical conditions, such as obesity, IR, type 2 diabetes, cardiovascular diseases, such as hyperlipidemia and coronary atherosclerosis, and neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease (30). Of these, IR is the common pathophysiological basis and risk factor of multiple metabolic diseases, which is the premise of the present study (31,32). HOMA-IR is a simple and useful indicator in the assessment of IR in epidemiological studies (33) and is widely used for the determination of glucose and insulin levels to reflect systemic IR (34).…”

Insulin-like Growth Factor Binding Proteins and Cellular Senescence Are Involved in the Progression of Non-Alcoholic Fatty Liver Disease and Fibrosis in a Mouse Model

“…The IGFBP superfamily has been related to insulin resistance [ 25 , 34 ], fat deposition, and other cellular processes, including senescence [ 9 ]. All these factors have a clear role in the development of NAFLD.…”

“…IGFBP-2 has been extensively studied in obesity, type 2 diabetes, insulin resistance, metabolic syndrome [ 34 , 40 , 41 , 42 , 43 ], and as an inductor of cancer [ 44 ]. In fact, this peptide has been suggested as a possible protector against obesity and insulin resistance [ 45 ].…”