Differential effects of bariatric surgery on plasma levels of ANGPTL3 and ANGPTL4

Nutr Metab Cardiovasc Dis. 2022 Nov;32(11):2647-2654. doi: 10.1016/j.numecd.2022.08.019. Epub 2022 Sep 1.

Abstract

Background and aim: Angiopoietin-like 3 (ANGPTL3) and 4 (ANGPTL4) are regulators of triglyceride storage and utilization. Bariatric surgery (BS) leads to profound changes in adipose tissue composition and energy metabolism. We evaluated the impact of BS on plasma levels of ANGPTL3 and ANGPTL4.

Methods and results: Twenty-seven subjects affected by morbid obesity with or without type 2 diabetes (T2D) underwent Roux-en-Y gastric bypass (RYGB) and 18 patients with advanced T2D received Biliopancreatic Diversion (BPD). Fasting ANGPTL proteins levels, insulin sensitivity (evaluated by euglycemic hyperinsulinemic clamp), total bile acids (TBA) and free fatty acids (FFA) were measured at baseline and 1 year after surgery. Both surgical procedures resulted in the loss of fat mass, improved glucose control, and a ∼2-fold increase of insulin sensitivity. ANGPTL4 levels decreased significantly with both RYGB (26.6 ± 0.6 to 24.4 ± 0.3 ng/mL, p = 0.001) and BPD (27.9 ± 1.5 to 24.0 ± 0.5 ng/mL, p = 0.003). In contrast, ANGPTL3 concentrations did not change after RYGB but rose following BPD (225 ± 20 to 300 ± 15 ng/mL, p = 0.003). By multiple regression analysis, changes after BS in ANGPTL4 were independently associated with changes in blood glucose, (p = 0.0169) whereas changes in ANGPTL3 were associated with variations in FFA (p = 0.008) and insulin sensitivity (p = 0.043).

Conclusion: Circulating ANGPTL4 is reduced by BS, probably due to the loss of fat mass and improved insulin sensitivity. Conversely, ANGPTL3 levels increased after BPD, but not after RYGB, presumably because of the metabolic changes induced by the malabsorptive effect of BPD.

Keywords: ANGPTL3; ANGPTL4; Bariatric surgery; Insulin sensitivity; Lipid metabolism; Type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiopoietin-Like Protein 3
  • Angiopoietin-Like Protein 4 / genetics
  • Angiopoietin-like Proteins / metabolism
  • Angiopoietins
  • Bariatric Surgery* / adverse effects
  • Bile Acids and Salts
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2* / diagnosis
  • Diabetes Mellitus, Type 2* / surgery
  • Fatty Acids, Nonesterified
  • Gastric Bypass* / adverse effects
  • Humans
  • Insulin Resistance*
  • Obesity, Morbid* / diagnosis
  • Obesity, Morbid* / surgery
  • Triglycerides

Substances

  • ANGPTL3 protein, human
  • ANGPTL4 protein, human
  • Angiopoietin-Like Protein 3
  • Angiopoietin-Like Protein 4
  • Angiopoietin-like Proteins
  • Angiopoietins
  • Bile Acids and Salts
  • Blood Glucose
  • Fatty Acids, Nonesterified
  • Triglycerides