Regulation of angiopoietin-like protein 8 expression under different nutritional and metabolic status

Abstract

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with increasing prevalence worldwide. Angiopoietin-like protein 8 (ANGPTL8), a member of the angiopoietin-like protein family, is involved in glucose metabolism, lipid metabolism, and energy homeostasis and believed to be associated with T2DM. Expression levels of ANGPTL8 are often significantly altered in metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD) and diabetes mellitus. Studies have shown that ANGPTL8, together with other members of this protein family, such as angiopoietin-like protein 3 (ANGPTL3) and angiopoietin-like protein 4 (ANGPTL4), regulates the activity of lipoprotein lipase (LPL), thereby participating in the regulation of triglyceride related lipoproteins (TRLs). In addition, members of the angiopoietin-like protein family are varyingly expressed among different tissues and respond differently under diverse nutritional and metabolic status. These findings may provide new options for the diagnosis and treatment of diabetes, metabolic syndromes and other diseases. In this review, the interaction between ANGPTL8 and ANGPTL3 or ANGPTL4, and the differential expression of ANGPTL8 responding to different nutritional and metabolic status during the regulation of LPL activity were reviewed.

Predictive values of ANGPTL8 on risk of all-cause mortality in diabetic patients: from the REACTION Study

“…The discrepancy in results may be due to heterogeneity of the participants. Furthermore, different ELISA kits detecting different ANGPTL8 cleavage products [40], ethnic group differences [41], genetic polymorphisms [42] or different nutrition statuses [3] may also contribute to the differences in study results. However, there are limited studies exploring the association of ANGPTL8 with CVD.…”

“…Several studies have suggested that ANGPTL8 closely interacts with and regulates ANGTPL3/4, affecting the levels of TG [1][2][3]. The long-term controversy regarding the role of ANGPTL8 in glucose and lipid metabolism has intrigued many researchers [4,5].…”

ANGPTL8 in metabolic homeostasis: more friend than foe?

“…speculated that this tissue-specific regulatory function of LPL would guide lipoprotein TG derived fatty acids away from muscle and into adipose tissue for storage [ 93 ]. In the previous studies of other researchers and review of our group, we have proposed that ANGPTL8 could guide the flow of postprandial TG by interacting with ANGPTL3 and ANGPTL4, and discussed its theoretical feasibility [ 17 ]. Following this, Chen et al .…”

“…On the other hand, ANGPTL8 is also involved in the regulation of appetite, that is, the increase of ANGPTL8 is related to the occurrence of anorexia, and neuropeptide Y-positive neurons in the dorsal medial hypothalamic nucleus may be involved in it [ 110 , 111 ]. The increased expression of ANGPTL8 caused by refeeding may feedback prevent the excessive feeding behaviour of the body, which was introduced in our previous review, so this article will not elaborate on it [ 17 ].…”

“…ANGPTL8 formed complexes with the other two respectively, and differentially regulated the LPL activity of adipose tissue and other oxidizing tissues, so that postprandial TG was directed into adipose tissue for storage. In the fasting state, the opposite expression regulation occurs, so that other oxidized tissues can obtain sufficient energy substrate sources [ 17 ]. Besides the regulation of lipid metabolism, several recent studies in animals have found that the effect of ANGPTL8 on improving insulin sensitivity [ 18 ].…”