Abstract
Follistatin-like 1 (FSTL1) is a secreted adipomyokine with a possible link to obesity; however, its connection to extreme obesity currently remains unknown. In order to analyze such association for the very first time, we employed a unique cohort of morbidly and super obese individuals with a mean BMI of 44.77 kg/m2 and measured the levels of circulating FSTL1. We explored the 3′ UTR of FSTL1 to locate a genetic variant which impairs microRNA binding. We located and investigated such SNP (rs1057231) in relation to the FSTL1 protein level, obesity status, and other body composition parameters. We observed a significant decline in FSTL1 level in obese subjects in comparison to nonobese ones. The evaluated SNP was found to correlate with FSTL1 only in nonobese subjects. The presented results were not affected by sex since both males and females expressed FSTL1 equally. We suggest that the FSTL1 decrease observed in extremely obese subjects is a result of adipogenesis reduction accompanied by a senescence of preadipocytes which otherwise willingly express FSTL1, increased adipocyte apoptosis, and epigenetic FSTL1 silencing.
Highlights
According to the latest WHO estimates for the European Union region, approximately 40–70% of adults are overweight and 10–30% are affected by obesity, i.e., an abnormal or excessive fat accumulation which constitutes a health risk
We identified no significant differences in systolic and/or diastolic blood pressure, triceptal, biceptal, supraspinal, and subscapular skinfold thickness, total body fat, total body water, hip circumference, waist circumference, and hip-waist ratio between OB and non-OB individuals with respect to follistatin-like 1 (FSTL1) levels
The FSTL1 protein has been described as an adipomyokine and it has recently received a substantial amount of attention, only a limited number of studies have provided a possible link to obesity, namely by pointing out its role in inflammation and adipocyte cell fate determination and describing its methylation status in obese individuals [5, 15, 16]
Summary
According to the latest WHO estimates for the European Union region, approximately 40–70% of adults are overweight and 10–30% are affected by obesity, i.e., an abnormal or excessive fat accumulation which constitutes a health risk. Obesity is considered to be one of the greatest public health challenges of the 21st century, which is evident from the fact that it consumes 4–7% of the total EU healthcare costs It is responsible for increased morbidity and mortality and enhances the risk of developing metabolic and nonmetabolic disorders such as type 2 diabetes mellitus, glucose intolerance, or chronic low-grade inflammation and cardiovascular disease, cancer, glomerulopathy, or bone fragility, respectively. It is a well-known fact that, far from being an inert fat deposit, adipose tissue constitutes an important and metabolically active endocrine organ which secretes proteins known as adipokines. Some adipokines, including, e.g., leptin, adiponectin, ghrelin, resistin, or interleukins have been studied extensively, the role of many others, including follistatin-like 1 (FSTL1), which has been suggested as linked to obesity, remains unclear [2, 3]
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