Abstract
Morbid obesity is associated with a state of chronic inflammation. Interleukin-1 family (IL-1F) cytokine members are produced by human adipose tissue in obesity. Whereas certain IL-1F members such as IL-1β or IL-18 are potently proinflammatory, others such as IL-1 receptor antagonist (IL-1Ra) or IL-37 (formerly IL-1F7) are antiinflammatory. The NLRP3 inflammasome plays a key role in the processing of bioactive IL-1β and IL-18. We investigated the effect of excessive weight loss on subcutaneous adipose tissue and liver expression of IL-1α, IL-1β, IL-18, IL-1Ra, IL-37 and NLRP3. Twenty-one severely obese patients undergoing laparoscopic adjustable gastric banding were studied. Tissue samples were collected before and 6 months after laparoscopic adjustable gastric banding surgery. mRNA expression of all studied IL-1F members, but especially of IL-37, was much higher in subcutaneous/visceral adipose tissue compared with their liver expression. Subcutaneous adipose tissue mRNA expression of IL-1β decreased significantly after extensive weight loss; expression of IL-18 and IL-1Ra did not change, whereas IL-37 expression increased. Weight loss led to a significant reduction in liver IL-1β, IL-18 and IL-1Ra expression, whereas hepatic IL-37 mRNA expression remained stable. Adipose/liver NLRP3 inflammasome and IL-1α expression were not affected by weight loss. Tissue expression of IL-1β, IL-18 and IL-37 were significantly higher in subcutaneous/visceral adipose tissue compared with the liver. In conclusion, expression of IL-1F members is more pronounced in adipose compared with liver tissue in patients with severe obesity. Excessive weight loss changes the adipose and liver expression profile of IL-1F members toward a more antiinflammatory direction.
Highlights
Obesity is characterized by a state of low-grade inflammation associated with increased cytokine production
Number and sex of subjects Age of subjects BMI Weight loss Aspartate amino transferase Alanine amino transferase γ-Glutamyl transferase Fasting glucosea Fasting insulinb HOMA index Glycated hemoglobin (%) Leukocytes (103/μL) C-reactive protein tivity; and (iii) weight loss leads to an increase in the adipose expression of certain antiinflammatory IL-1 family (IL-1F) members such as IL-37
A 28-day diet with an average weight loss of 6 kg was associated with an increase of mRNA adipose tissue expression of both IL-10 and IL-1 receptor antagonist (IL-1Ra) [21]
Summary
Obesity is characterized by a state of low-grade inflammation associated with increased cytokine production. Stienstra et al [7] recently demonstrated that caspase-1 and IL-1β activity increase in adipose tissue of dietary as well as genetically obese mice. Surgery-induced weight loss was associated with a significant improvement in laboratory parameters, such as alanine aminotransferase, γ-glutamyl transferase (GGT) and C-reactive protein (CRP) levels (see Table 1).
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