The possible role of antimicrobial proteins in obesity-associated immunologic alterations

Abstract

Currently, obesity-associated metabolic disturbances are envisioned as chronic inflammatory processes, characterized by activation of both innate and adaptive immunity. Although the features of chronic inflammation in obese subjects are clearly defined, the signals and mechanisms that trigger chronic inflammation are not well understood. Recent studies suggest an imbalance in circulating antimicrobial proteins as a possible cause of obesity-associated metabolic disturbances and insulin resistance. This imbalance promotes a relative failure in the capacity of buffering external insults and might cause the onset of chronic inflammation and immunologic alterations in obesity. Here, we review the current literature on the possible role of circulating antimicrobial proteins in obesity-associated immunologic alterations.

Keywords::

• adipose tissue
• antimicrobial proteins
• chronic inflammation
• innate immunity
• metabolic endotoxemia
• obesity

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Obesity is closely associated with a chronic low-grade inflammation, characterized by activation of both innate and adaptive immunity.

• Obesity leads to immunologic alterations in metabolic tissues, such as adipose tissue, liver and muscle.

• Obesity-associated metabolic dysfunction also leads to systemic immunologic alterations, which is associated with an unbalanced production and/or secretion of antimicrobial proteins.

• sCD14 exerts protective effects against obesity-associated metabolic disturbances, possibly, blunting lipopolysaccharide proinflammatory effects.

• Serum and tissue lipopolysaccharide-binding protein (LBP) concentration is a potential marker in the onset and progression of obesity and its associated metabolic disturbances.

• Lactoferrin administration exerts positive effects in the prevention and improvement of obesity-associated metabolic disturbances.

• LBP and lactoferrin gene and protein expression has been detected in mouse and human adipose tissue at substantial levels, being specifically expressed in adipocytes.

• Adipocyte dysfunction promotes the development of systemic lipotoxicity, insulin resistance and other metabolic disturbances.

• Adipose tissue LBP gene and protein expression is significantly associated with obesity, adipose tissue inflammation and metabolic deterioration, whereas its depletion improves adipocyte function.

• Decreased adipocyte lactoferrin mRNA and protein levels are associated with obesity, adipose tissue inflammation and adipocyte dysfunction.

• Both the administration of PPARγ agonists and the diet- or bariatric surgery-induced weight loss might be useful to regulate the biosynthesis of antimicrobial proteins.

Notes