Abstract
ObjectiveFetuin B is a steatosis-responsive hepatokine that causes glucose intolerance in mice, but the underlying mechanisms remain incompletely described. This study aimed to elucidate the mechanisms of action of fetuin B by investigating its putative effects on white adipose tissue metabolism.MethodsFirst, fetuin B gene and protein expression was measured in multiple organs in mice and in cultured adipocytes. Next, the authors performed a hyperinsulinemic-euglycemic clamp in mice and in humans to examine the link between white adipose tissue fetuin B content and indices of insulin sensitivity. Finally, the effect of fetuin B on inflammation was investigated in cultured adipocytes by quantitative polymerase chain reaction and full RNA sequencing.ResultsThis study demonstrated in adipocytes and mice that fetuin B was produced and secreted by the liver and taken up by adipocytes and adipose tissue. There was a strong negative correlation between white adipose tissue fetuin B content and peripheral insulin sensitivity in mice and in humans. RNA sequencing and polymerase chain reaction analysis revealed that fetuin B induced an inflammatory response in adipocytes.ConclusionsFetuin B content in white adipose tissue strongly associated with peripheral insulin resistance in mice and humans. Furthermore, fetuin B induced a proinflammatory response in adipocytes, which might drive peripheral insulin resistance.
Original language | English |
---|---|
Pages (from-to) | 517-527 |
Number of pages | 11 |
Journal | Obesity |
Volume | 32 |
Issue number | 3 |
Early online date | 1 Dec 2023 |
DOIs | |
Publication status | Published - Mar 2024 |
Keywords
- OBESE HUMANS
- GLUCOSE
- SENSITIVITY
- STEATOSIS