Differential Impact of Weight Loss and Glycemic Control on Inflammasome Signaling

Obesity (Silver Spring). 2020 Mar;28(3):609-615. doi: 10.1002/oby.22734. Epub 2020 Feb 5.

Abstract

Objective: Interleukin (IL)-1β is involved in obesity-associated inflammation and in the pathogenesis of type 2 diabetes (T2D) mellitus. Our aim was to correlate serum IL-1β and caspase-1 levels with weight loss, glucose metabolism, and insulin resistance (IR) after bariatric surgery.

Methods: A total of 32 patients with morbid obesity and T2D (Ob-T2D) and 29 patients with morbid obesity and normal glucose tolerance (Ob-NGT), treated by Roux-en-Y gastric bypass, were studied before and 1 year after surgery. Sixteen healthy individuals served as a control (HC) group. IR was assessed by the oral glucose insulin sensitivity method. Plasma IL-1β levels and caspase-1 were measured.

Results: Presurgery BMI was similar in Ob-NGT and Ob-T2D. IR was progressively impaired in Ob-NGT and Ob-T2D (P < 0.0001). Fasting plasma IL-1β and caspase-1 levels were lower in HCs than in patients with Ob-NGT or Ob-T2D (P < 0.02; P = 0.05), and both were inversely correlated with IR (P = 0.01; P = 0.02). After surgery, BMI decreased and IR improved to a similar extent in Ob-NGT and Ob-T2D (P < 0.0001). Plasma caspase-1 concentrations normalized in both groups (P < 0.0001), whereas plasma IL-1β levels normalized only in Ob-NGT.

Conclusions: Plasma IL-1β and caspase-1 levels were inversely correlated with IR. Caspase-1 levels normalized after weight loss, whereas IL-1β normalized only in people without T2D, suggesting the persistence of a systemic inflammatory condition in people with T2D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism*
  • Cell Differentiation
  • Female
  • Gastric Bypass / methods*
  • Healthy Volunteers
  • Humans
  • Inflammasomes / genetics*
  • Interleukin-1beta / genetics*
  • Male
  • Middle Aged
  • Obesity, Morbid / genetics*
  • Signal Transduction
  • Weight Loss / genetics*

Substances

  • Blood Glucose
  • IL1B protein, human
  • Inflammasomes
  • Interleukin-1beta