TY - JOUR

T1 - Obesity and Low-Grade Inflammation Increase Plasma Follistatin-Like 3 in Humans

AU - Brandt, Claus

AU - Pedersen, Maria

AU - Rinnov, Anders

AU - Andreasen, Anne S

AU - Møller, Kirsten

AU - Hojman, Pernille

AU - Pedersen, Bente K

AU - Plomgaard, Peter

PY - 2014

Y1 - 2014

N2 - BACKGROUND: Rodent models suggest that follistatin-like 3 (fstl3) is associated with diabetes and obesity. In humans, plasma fstl3 is reduced with gestational diabetes. In vitro, TNF-α induces fstl3 secretion, which suggests a link to inflammation.OBJECTIVE: To elucidate the association between plasma fstl3 and obesity, insulin resistance, and low-grade inflammation in humans.STUDY DESIGN: Plasma fstl3 levels were determined in a cross-sectional study including three groups: patients with type 2 diabetes, impaired glucose tolerance, and healthy controls. In addition, lipopolysaccharide (LPS), TNF-α, or interleukin-6 (IL-6) as well as a hyperinsulinemic euglycemic clamp were used to examine if plasma fstl3 was acutely regulated in humans.RESULTS: Plasma fstl3 was increased in obese subjects independent of glycemic state. Moreover, plasma fstl3 was positively correlated with fat mass, plasma leptin, fasting insulin, and HOMA B and negatively with HOMA S. Furthermore plasma fstl3 correlated positively with plasma TNF-α and IL-6 levels. Infusion of LPS and TNF-α, but not IL-6 and insulin, increased plasma fstl3 in humans.CONCLUSION: Plasma fstl3 is increased in obese subjects and associated with fat mass and low-grade inflammation. Furthermore, TNF-α increased plasma fstl3, suggesting that TNF-α is one of the inflammatory drivers of increased systemic levels of fstl3.

AB - BACKGROUND: Rodent models suggest that follistatin-like 3 (fstl3) is associated with diabetes and obesity. In humans, plasma fstl3 is reduced with gestational diabetes. In vitro, TNF-α induces fstl3 secretion, which suggests a link to inflammation.OBJECTIVE: To elucidate the association between plasma fstl3 and obesity, insulin resistance, and low-grade inflammation in humans.STUDY DESIGN: Plasma fstl3 levels were determined in a cross-sectional study including three groups: patients with type 2 diabetes, impaired glucose tolerance, and healthy controls. In addition, lipopolysaccharide (LPS), TNF-α, or interleukin-6 (IL-6) as well as a hyperinsulinemic euglycemic clamp were used to examine if plasma fstl3 was acutely regulated in humans.RESULTS: Plasma fstl3 was increased in obese subjects independent of glycemic state. Moreover, plasma fstl3 was positively correlated with fat mass, plasma leptin, fasting insulin, and HOMA B and negatively with HOMA S. Furthermore plasma fstl3 correlated positively with plasma TNF-α and IL-6 levels. Infusion of LPS and TNF-α, but not IL-6 and insulin, increased plasma fstl3 in humans.CONCLUSION: Plasma fstl3 is increased in obese subjects and associated with fat mass and low-grade inflammation. Furthermore, TNF-α increased plasma fstl3, suggesting that TNF-α is one of the inflammatory drivers of increased systemic levels of fstl3.

KW - Adiponectin

KW - Adult

KW - Cross-Sectional Studies

KW - Follistatin-Related Proteins

KW - Humans

KW - Inflammation

KW - Insulin

KW - Interleukin-6

KW - Leptin

KW - Lipopolysaccharides

KW - Male

KW - Obesity

KW - Tumor Necrosis Factor-alpha

U2 - 10.1155/2014/364209

DO - 10.1155/2014/364209

M3 - Journal article

C2 - 25104880

VL - 2014

SP - 1

EP - 10

JO - Mediators of Inflammation

JF - Mediators of Inflammation

SN - 0962-9351

M1 - 364209

ER -