Abstract
Research in recent years on peroxisome proliferator-activated receptor (PPAR)β/δ indicates that it plays a key role in the maintenance of energy homeostasis, both at the cellular level and within the organism as a whole. PPARβ/δ activation might help prevent the development of metabolic disorders, including obesity, dyslipidaemia, type 2 diabetes mellitus and non-alcoholic fatty liver disease. This review highlights research findings on the PPARβ/δ regulation of energy metabolism and the development of diseases related to altered cellular and body metabolism. It also describes the potential of the pharmacological activation of PPARβ/δ as a treatment for human metabolic disorders.
Highlights
Acquired metabolic disorders, obesity and its associated co-morbidities currently pose a risk to human health on a global scale
These metabolic disorders are closely related to adipose tissue dysfunction, one of the primary defects observed in obesity that may link this condition to its co-morbidities such as non-alcoholic fatty liver disease (NAFLD), atherogenic dyslipidaemia, type 2 diabetes mellitus and cardiovascular disease [1,2,3]
We have previously reported that PPARβ/δ activation prevents the attenuation of the insulin signalling pathway in human liver cells by preventing IL-6-induced signal transducer and activator of transcription 3 (STAT3) activation through a mechanism that inhibits ERK1/2 phosphorylation and suppresses the reduction in phospho-AMP kinase (AMPK) levels [64]
Summary
Obesity and its associated co-morbidities currently pose a risk to human health on a global scale. The major physiological functions of PPARβ/δ result from its activity as a transcription factor, modulating the expression of specific target genes. Through this mechanism, PPARβ/δ regulates lipid metabolism and glucose homeostasis [8,9,10,11]. PPARβ/δ expression is reduced in both the subcutaneous and in visceral adipose tissues of morbidly obese patients compared to non-obese subjects [27]. This might result in adipose tissue dysregulation since PPARβ/δ has anti-inflammatory effects in white adipose tissue. Consistent with the effects of PPARβ/δ in adipose tissue, it has been reported that overweight patients with mixed dyslipidaemia who were administered the PPARβ/δ agonist MBX-8025 for 8 weeks presented favourable trends in their body fat percentage, lean body mass and waist circumference, the differences did not reach statistical significance [30]
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