Figure 1

A Resurgence of the Idea of Hypertriglyceridemia and Lower Serum (HDL-C) as Predictive Factors for Insulin Resistance (IR) & Type 2 Diabetes Mellitus Development: A Narrative Review

Kulvinder Kochar Kaur*

Published: 24 July, 2025 | Volume 9 - Issue 1 | Pages: 001-012

niogb-aid1022-g001

Figure 1:

Courtesy ref no-51-Lipoprotein lipase (LPL) complex bound to the capillary endothelial cell surface. LPL bound to endothelial cells is a key enzyme for hydrolysis of triglyceride (TG) into free fatty acids (FFA) and monoglyceride. Head‐to‐tail homodimer formation was thought to be critical for LPL secretion and the maintenance of the enzymatic activity, whereas recent data suggested that LPL is synthesized and secreted as a monomer, and chaperoned through the biosynthesis pathway to maintain its mature structure. During the biosynthesis of LPL in parenchymal cells, such as adipocytes and myocytes, LPL is chaperoned by lipase maturation factor 1 (LMF1) and Sel‐1 suppressor of Lin‐12‐Like 1 (SEL1L), and secreted through the trans‐Golgi network (pink ribbon model). LPL next binds to heparan sulfate proteoglycan and is stabilized in the extracellular matrix in the interstitial space, and glycocalyx on the endothelial cells and parenchymal cells. LPL next forms the complex with glycosylphosphatidylinositol‐anchored high‐density lipoprotein binding protein 1 (GPIHBP1; brown ribbon model), and they are shuttled to the capillary lumen of the endothelial cells. Apolipoprotein C‐II (APOC2) on the chylomicron and very low‐density lipoprotein is a critical factor for LPL hydrolysis enzymatic activity, whereas APOC1 and APOC3 compete with LPL for binding to lipid emulsion particles. The binding of angiopoietin‐like protein (ANGPTL)4 to LPL adjacent to the catalytic cavity triggers the unfolding of LPL's hydrolase domain, resulting in the irreversible collapse of the catalytic cavity and loss of LPL activity. ANGPTL3– ANGPTL8 regulates the lipid intake in the heart (H), skeletal muscle (M), and brown adipose tissue (BAT) by the inhibition of LPL in the fed state, whereas ANGPTL8 in white adipose tissues (WAT) attenuates LPL inhibition by ANGPTL4 to promote triglyceride (TG)‐rich lipoprotein processing. ER, endoplasmic reticulum.

Read Full Article HTML DOI: 10.29328/journal.niogb.1001022 Cite this Article Read Full Article PDF

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