elafin and Obesity

Secretory leukocyte protease inhibitor (SLPI), a serine protease inhibitor, which was most commonly examined in mucosal fluids such as saliva, is a versatile molecule and plays non-redundant roles. In addition to its anti-protease activity, SLPI has been shown to express anti-bacterial, anti-viral, anti-fungal, and anti-inflammatory properties as well as participating in innate and adaptive immune responses, most of which has been well documented. Recently, it is reported that SLPI is expressed in adipocytes and adipose tissue where it could play an important feedback role in the resolution of inflammation. Furthermore, circulating SLPI has been shown to correlate with progressive metabolic dysfunction. Moreover, adenoviral gene delivery of elafin and SLPI attenuates nuclear factor-κB-dependent inflammatory responses of human endothelial cells and macrophages to atherogenic stimuli. This review contributes to unraveling the protective role of SLPI in obesity-related atherosclerosis development, and the potential role in preventing arterial plaque rupture.

Topics: Adipocytes; Adipose Tissue; Anti-Inflammatory Agents; Antioxidants; Atherosclerosis; Elafin; Humans; Inflammation; Obesity; Plaque, Atherosclerotic; Secretory Leukocyte Peptidase Inhibitor

Elafin is an antimicrobial and anti-inflammatory protein. We hypothesize that elafin expression correlates with diabetes. Among non-diabetic and prediabetic groups, men have significantly higher serum elafin levels than women. Men with type 2 diabetes mellitus (T2DM) have significantly lower serum elafin levels than men without T2DM. Serum elafin levels are inversely correlated with fasting blood glucose and hemoglobin A1c levels in men with T2DM, but not women with T2DM. Lentiviral elafin overexpression inhibited obesity, hyperglycemia, and liver steatosis in high-fat diet (HFD)-treated male mice. Elafin-overexpressing HFD-treated male mice had increased serum leptin levels, and serum exosomal miR181b-5p and miR219-5p expression. Transplantation of splenocytes and serum exosomes from elafin-overexpressing HFD-treated donor mice reduced food consumption and fat mass, and increased adipose tissue leptin mRNA expression in HFD-treated recipient mice. Elafin improved leptin sensitivity via reduced interferon-gamma expression and induced adipose leptin expression via increased miR181b-5p and miR219-5p expression. Subcutaneous and oral administration of modified elafin inhibited obesity, hyperglycemia, and liver steatosis in the HFD-treated mice. Circulating elafin levels are associated with hyperglycemia in men with T2DM. Elafin, via immune-derived miRNAs and cytokine, activates leptin sensitivity and expression that subsequently inhibit food consumption, obesity, hyperglycemia, and liver steatosis in HFD-treated male mice.

Topics: Adipose Tissue; Animals; Cytokines; Diet, High-Fat; Disease Models, Animal; Eating; Elafin; Fatty Liver; Female; Gene Expression; Humans; Hyperglycemia; Interferon-gamma; Leptin; Male; Mice, Inbred C57BL; Obesity; Sex Characteristics