Angiopoietin-like protein 3 and 4 in obesity, type 2 diabetes mellitus, and malnutrition: the effect of weight reduction and realimentation

Abstract

BackgroundAngiopoietin-like proteins (ANGPTLs) 3 and 4 are circulating factors that participate in the regulation of lipid and glucose metabolism.Subjects and methodsWe measured serum ANGPTL3 and 4 levels in 23 patients with obesity, 40 patients with obesity and type 2 diabetes mellitus (T2DM), 22 patients with anorexia nervosa (AN), 15 subjects undergoing 72-h fasting, and 12 patients with short bowel syndrome (SBS), and their changes after very-low-calorie diet (VLCD), bariatric surgery, partial realimentation, acute fasting, and parenteral nutrition in order to assess their possible role in metabolic regulations.ResultsSerum ANGPTL4 levels were higher in obese subjects without/with T2DM (94.50 ± 9.51 and 134.19 ± 7.69 vs. 50.34 ± 4.22 ng/ml, p < 0.001) and lower in subjects with AN relative to healthy control subjects (38.22 ± 4.48 vs. 65.80 ± 7.98 ng/ml, p = 0.002), while serum ANGPTL3 levels demonstrated inverse tendency. Nutritional status had no effect on ANGPTL3 and 4 mRNA expression in adipose tissue. Fasting decreased ANGPTL3 and increased ANGPTL4 levels, while VLCD reduced only ANGPTL3. Bariatric surgery and realimentation of AN or SBS patients had no effect on either ANGPTL. Multiple regression analysis identified BMI as an independent predictor of ANGPTL3; and BMI and HbA1c as independent predictors of ANGPTL4, respectively.ConclusionsTaken together, our data suggest that serum ANGPTL3 and 4 levels are influenced by nutritional status and fasting and could be involved in the metabolic disturbances present in obesity and AN.

Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases

“…The practice of fasting combined with physical exercise is indicated as an important inducer of ANGPTL4 expression and may be beneficial to those with high serum levels of long chain fatty acids (Ingerslev et al, 2017 ). In addition, an increase in serum ANGPTL4 in obese patients (with or without T2DM) was observed, and the same was observed in patients who underwent bariatric surgery and in fasting patients, while it was reduced in patients with anorexia (Cinkajzlova et al, 2018 ). However, even with published data indicating a role for ANGPTL4 in obesity, and glucose intolerance (Morris, 2018 ), this protein is still poorly studied and there is much about its therapeutic role that needs to be further investigated.…”

“…Angiopoietin-like protein (ANGPTL) is a group of proteins that can be secreted by the AT, SkM, intestinal, and liver cells and is responsible for several processes, among them energy metabolism, and TG turnover modulation in AT and the regulation of blood glucose levels (Ingerslev et al, 2017 ; Popova et al, 2018 ). Despite the name, ANGPTLs are not specific ligands for angiopoietin, but are named after the structural similarity with this protein (Cinkajzlova et al, 2018 ).…”

“…Specifically, plasma ANGPTL4 acts on myotubes, and is well-established as a myokine derived from physical exercise (exercise factor; Raschke and Eckel, 2013 ; Ingerslev et al, 2017 ). The performance of this protein is related to several physiological processes, among them are insulin sensitivity, lipid metabolism, adipogenesis (Cinkajzlova et al, 2018 ), and the increase of circulating fatty acids, which are generated mainly by chronic caloric restrictions, fasting, and aerobic physical training (Raschke and Eckel, 2013 ).…”

Angiopoietin-like protein 4 (ANGPTL4) is related to gestational weight gain in pregnant women with obesity

“…Human studies produced inconsistent findings regarding the notion of ANGPTL4 to act as a signal preventing fat storage, and there are also studies that failed to find an association between ANGPTL4 and TAG or non-esterified fatty acid (NEFA) concentrations 11 , 12 . Moreover, serum ANGPTL4 concentrations has been found higher in obese subjects without/with type 2 diabetes mellitus relative to control subjects 13 , and variants of ANGPTL4 are associated with lower plasma TAG and higher waist circumference 14 . Recently, it has been found that ANGPTL4 is upregulated in human adipocytes in response to hypoxia 15 – 17 , and studies using microarray-based technology have reported that the expression of ANGPTL4 is significantly upregulated in obesity, in early 18 and late phases of adipocyte differentiation 19 , as well as in fat samples from obese subjects 20 , 21 .…”

ANGPTL4 supports glutamine metabolism and promotes fatty acid oxidation in nonsmall cell lung cancer cells

“…Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional cytokine that is involved in both angiogenesis and metastasis [7]. ANGPTL4 exhibits structural similarity to the multifunctional angiopoietins, which are involved in glucose homeostasis, lipid metabolism, angiogenesis, in ammation, and tumor progression and metastasis [8][9][10]. ANGPTL4 serves an important role in the tumor microenvironment, especially that which is hypoxia-induced.…”