Docosahexaenoic acid suppresses expression of adipogenic tetranectin through sterol regulatory element-binding protein and forkhead box o protein in pigs
Journal
Nutrients
Journal Volume
13
Journal Issue
7
Date Issued
2021
Author(s)
Abstract
Tetranectin (TN), a plasminogen-binding protein originally involved in fibrinolysis and bone formation, was later identified as a secreted adipokine from human and rat adipocytes and positively correlated with adipogenesis and lipid metabolism in adipocytes. To elucidate the nutritional regulation of adipogenic TN from diets containing different sources of fatty acids (saturated, n-6, n-3) in adipocytes, we cloned the coding region of porcine TN from a cDNA library and analyzed tissue expressions in weaned piglets fed with 2% soybean oil (SB, enriched in n-6 fatty acids), docosahexaenoic acid oil (DHA, an n-3 fatty acid) or beef tallow (BT, enriched in saturated and n-9 fatty acids) for 30 d. Compared with tissues in the BT-or SB-fed group, expression of TN was reduced in the adipose, liver and lung tissues from the DHA-fed group, accompanied with lowered plasma levels of triglycerides and cholesterols. This in vivo reduction was also confirmed in porcine primary differentiated adipocytes supplemented with DHA in vitro. Then, promoter analysis was performed. A 1956-bp putative porcine TN promoter was cloned and transcription binding sites for sterol regulatory-element binding protein (SREBP)-1c or forkhead box O proteins (FoxO) were predicted on the TN promoter. Mutating binding sites on porcine TN promoters showed that transcriptional suppression of TN by DHA on promoter activity was dependent on specific response elements for SREBP-1c or FoxO. The inhibited luciferase promoter activity by DHA on the TN promoter coincides with reduced gene expression of TN, SREBP-1c, and FoxO1 in human embryonic kidney HEK293T cells supplemented with DHA. To conclude, our current study demonstrated that the adipogenic TN was negatively regulated by nutritional modulation of DHA both in pigs in vivo and in humans/pigs in vitro. The transcriptional suppression by DHA on TN expression was partly through SREBP-1c or FoxO. Therefore, down-regulation of adipogenic tetranectin associated with fibrinolysis and adipogenesis may contribute to the beneficial effects of DHA on ameliorating obesity-induced metabolic syndromes such as atherosclerosis and adipose dysfunctions. ? 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Subjects
Adipose tissues
Docosahexaenoic acid (DHA)
Forkhead box O protein (FoxO)
Pigs
Sterol regulatory element-binding protein-1c (SREBP-1c)
Tetranectin
cholesterol
docosahexaenoic acid
sterol regulatory element binding protein
sterol regulatory element binding protein 1c
tetranectin
transcription factor FOXO
triacylglycerol
forkhead transcription factor
lectin
adipocyte
adipogenesis
animal cell
animal experiment
animal tissue
Article
binding site
cholesterol blood level
controlled study
DNA library
embryo
gene expression
human
human cell
in vitro study
male
nonhuman
pig
promoter region
protein expression
triacylglycerol blood level
animal
drug effect
fibrinolysis
genetics
HEK293 cell line
metabolism
nutrition
Adipocytes
Adipogenesis
Animals
Docosahexaenoic Acids
Fibrinolysis
Forkhead Transcription Factors
HEK293 Cells
Humans
Lectins, C-Type
Nutritional Physiological Phenomena
Sterol Regulatory Element Binding Proteins
Swine
SDGs
Type
journal article