Regulation of visceral adipose tissue‐derived serine protease inhibitor by nutritional status, metformin, gender and pituitary factors in rat white adipose tissue

Abstract

Visceral adipose tissue-derived serine protease inhibitor (vaspin) is a recently discovered adipocytokine mainly secreted from visceral adipose tissue, which plays a main role in insulin sensitivity. In this study, we have investigated the regulation of vaspin gene expression in rat white adipose tissue (WAT) in different physiological (nutritional status, pregnancy, age and gender) and pathophysiological (gonadectomy, thyroid status and growth hormone deficiency) settings known to be associated with energy homeostasis and alterations in insulin sensitivity. We have determined vaspin gene expression by real-time PCR. Vaspin was decreased after fasting and its levels were partially recovered after leptin treatment. Chronic treatment with metformin increased vaspin gene expression. Vaspin mRNA expression reached the highest peak at 45 days in both sexes after birth and its expression was higher in females than males, but its levels did not change throughout pregnancy. Finally, decreased levels of growth hormone and thyroid hormones suppressed vaspin expression. These findings suggest that WAT vaspin mRNA expression is regulated by nutritional status, and leptin seems to be the nutrient signal responsible for those changes. Vaspin is influenced by age and gender, and its expression is increased after treatment with insulin sensitizers. Finally, alterations in pituitary functions modify vaspin levels. Understanding the molecular mechanisms regulating vaspin will provide new insights into the pathogenesis of the metabolic syndrome.

Vaspin is related to gender, puberty and deteriorating insulin sensitivity in children

“…In the insulin-resistant group, vaspin significantly declined during the oGTT, somehow inversely mirroring the course of insulin. This finding is coherent with the observation of a meal-related decline in vaspin levels 11,16 and may indicate that glucose and/or insulin may have acute suppressive effects of circulating vaspin levels and/or that food-related effects such as vagal activation are involved. Tan et al 10 identified glucose as a vaspin-releasing agent, at least in human omental adipose tissue explants, whereas Loeffelholz et al 17 observed a (non-significant) decrease of serum vaspin under conditions of euglycemic hyperinsulinemia.…”

“…17,18 One explanation might be that some studies included subjects with an extreme phenotype in terms of insulin resistance and thus the metabolic effects could have overcome any potential impact of sex steroids on serum vaspin. Considering that children present a phase early in the pathological career of obesity-related comorbidities, but on the other hand are free of possibly interfering drugs, such as oral antidiabetic medications, 10,16 our data may support the conclusion of an adaptive response of vaspin to impaired glucose metabolism. 3 The association of vaspin with metabolic parameters was robustly significant in our cohort, independent from BMI SDS and hence the degree of obesity.…”

“…In rats, high thyroid hormone levels suppressed vaspin levels. 16 However, our study design did not allow interpreting this association.…”

“…5 Consistently, WAT vaspin expression was unchanged in gonadectomized rats. 16 In our cohort, there was no correlation between the puberty-related sex steroids, estradiol, or testosterone. Hence, so far it is unclear where this sexual dimorphism comes from, but the association of vaspin with female sex and age must be considered in clinical studies on vaspin.…”

“…Besides expression in WAT, we identified vaspin mRNA expression in the liver and potentially in the skin and the pancreas. Most studies found higher vaspin levels in adult women compared with men, 6,8,[16][17][18] whereas others did not. 7,9,19 According to our data, vaspin increased with puberty in girls, but not in boys.…”