Treatment with TUG891, a free fatty acid receptor 4 agonist, restores adipose tissue metabolic dysfunction following chronic sleep fragmentation in mice
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Treatment with TUG891, a free fatty acid receptor 4 agonist, restores adipose tissue metabolic dysfunction following chronic sleep fragmentation in mice. / Gozal, D; Qiao, Z; Almendros, I; Zheng, J; Khalyfa, A; Shimpukade, B; Ulven, T.
In: International Journal of Obesity, Vol. 40, No. 7, 2016, p. 1143-1149.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Treatment with TUG891, a free fatty acid receptor 4 agonist, restores adipose tissue metabolic dysfunction following chronic sleep fragmentation in mice
AU - Gozal, D
AU - Qiao, Z
AU - Almendros, I
AU - Zheng, J
AU - Khalyfa, A
AU - Shimpukade, B
AU - Ulven, T
PY - 2016
Y1 - 2016
N2 - BACKGROUND: Sleep fragmentation (SF), a frequent occurrence in multiple sleep and other diseases leads to increased food intake and insulin resistance via increased macrophage activation and inflammation in visceral white adipose tissue (VWAT). Free fatty acid receptor 4 (FFA4) is reduced in pediatric sleep apnea patients and FFA4 agonists have been proposed in the treatment of obesity and metabolic dysfunction.METHODS: Male mice were subjected to SF exposures for 6 weeks, and treated during the last 2 weeks with either TUG891, a potent and selective FFA4 agonist, or vehicle (Veh). Glucose and insulin tolerance tests and VWAT insulin sensitivity tests were conducted (phosphorylated AKT/total AKT), along with flowcytometric assessments of VWAT macrophage polarity, and T-cell lymphocyte subsets.RESULTS: SF-TUG891 mice showed reduction in food consumption, weight gain, and VWAT mass. Furthermore, TUG891 treatment ameliorated GTT and ITT responses and increased VWAT p-AKT/AKT responses to insulin. Increases in M1/M2 macrophages and decreased Treg counts in VWAT associated with SF were markedly improved by TUG891, and VWAT macrophages from TUG891-treated mice had markedly attenuated insulin reistance effects on naïve cultured adipocytes.,CONCLUSIONS: Treatment with a FFA4 agonist reverses SF-induced food intake increases and gains in body weight, and significantly attenuates VWAT inflammation and insulin resistance. Thus, interventional dietary or pharmaceutical strategies aimed at increasing FFA4 activity may serve as potentially useful adjunctive therapies for sleep disorders accompanied by metabolic morbidity.International Journal of Obesity accepted article preview online, 16 March 2016. doi:10.1038/ijo.2016.37.
AB - BACKGROUND: Sleep fragmentation (SF), a frequent occurrence in multiple sleep and other diseases leads to increased food intake and insulin resistance via increased macrophage activation and inflammation in visceral white adipose tissue (VWAT). Free fatty acid receptor 4 (FFA4) is reduced in pediatric sleep apnea patients and FFA4 agonists have been proposed in the treatment of obesity and metabolic dysfunction.METHODS: Male mice were subjected to SF exposures for 6 weeks, and treated during the last 2 weeks with either TUG891, a potent and selective FFA4 agonist, or vehicle (Veh). Glucose and insulin tolerance tests and VWAT insulin sensitivity tests were conducted (phosphorylated AKT/total AKT), along with flowcytometric assessments of VWAT macrophage polarity, and T-cell lymphocyte subsets.RESULTS: SF-TUG891 mice showed reduction in food consumption, weight gain, and VWAT mass. Furthermore, TUG891 treatment ameliorated GTT and ITT responses and increased VWAT p-AKT/AKT responses to insulin. Increases in M1/M2 macrophages and decreased Treg counts in VWAT associated with SF were markedly improved by TUG891, and VWAT macrophages from TUG891-treated mice had markedly attenuated insulin reistance effects on naïve cultured adipocytes.,CONCLUSIONS: Treatment with a FFA4 agonist reverses SF-induced food intake increases and gains in body weight, and significantly attenuates VWAT inflammation and insulin resistance. Thus, interventional dietary or pharmaceutical strategies aimed at increasing FFA4 activity may serve as potentially useful adjunctive therapies for sleep disorders accompanied by metabolic morbidity.International Journal of Obesity accepted article preview online, 16 March 2016. doi:10.1038/ijo.2016.37.
U2 - 10.1038/ijo.2016.37
DO - 10.1038/ijo.2016.37
M3 - Journal article
VL - 40
SP - 1143
EP - 1149
JO - International Journal of Obesity
JF - International Journal of Obesity
SN - 0307-0565
IS - 7
ER -
ID: 189161853