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

Anna Cinkajzlová,Petra Kaválková,Martin Haluzík,Hana Papežová,Pavel Trachta,Zdeňka Lacinová,Miloš Mráz,Denisa Haluzíková,Jana Kloučková,Helena Kratochvílová,Jarmila Křížová,Jan Škrha

doi:10.1038/s41387-018-0032-2

Anna Cinkajzlová, Petra Kaválková + Show 10 more

Open Access

https://doi.org/10.1038/s41387-018-0032-2

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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.

Highlights

Angiopoietin-like proteins (ANGPTLs) 3 and 4 are members of the ANGPTL protein family namedNutrition and DiabetesCinkajzlová et al Nutrition and Diabetes (2018)8:21invasion[7,8] as well as regulation of lipid and glucose metabolism[9,10].ANGPTL3 and 4 are released into systemic circulation primarily from the liver and act in a number of tissues, including white adipose tissue (WAT)[2]
Taken 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 anorexia nervosa (AN)
ANGPTL3 is upregulated by liver X receptor, which serves as a sensor of cholesterol metabolism and lipid biosynthesis[15,16], while ANGPTL4 is a downstream target of peroxisome proliferator-activated receptors that modulate lipid metabolism, insulin sensitivity, and adipocyte differentiation

Summary

Introduction

ANGPTL3 and 4 are released into systemic circulation primarily from the liver and act in a number of tissues, including white adipose tissue (WAT)[2] In spite of their similar structure with 31% amino-acid sequence identity[11], their biological actions differ according to underlying conditions[12,13,14]. ANGPTL3 is upregulated by liver X receptor, which serves as a sensor of cholesterol metabolism and lipid biosynthesis[15,16], while ANGPTL4 is a downstream target of peroxisome proliferator-activated receptors that modulate lipid metabolism, insulin sensitivity, and adipocyte differentiation. Both ANGPTL3 and ANGPTL4 inhibit lipoprotein lipase (LPL) and stimulate lipolysis[17]. Angiopoietin-like proteins (ANGPTLs) 3 and 4 are circulating factors that participate in the regulation of lipid and glucose metabolism

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Conclusion