Since the removal of thiazolidinediones (TZDs) from the market, researchers have been exploring alternative anti-diabetic drugs that target PPARγ without causing adverse effects while promoting insulin sensitization by blocking serine 273 phosphorylation (Ser273 or S273). Nonetheless, the underlying mechanisms of the relationship between insulin resistance and S273 phosphorylation are still largely unknown, except for the involvement of growth differentiation factor (GDF3) regulation in the process. To further investigate potential pathways, we generated a whole organism mouse line with a single S273A mutation (KI) that blocks the occurrence of its phosphorylation.
View Article and Find Full Text PDFObesity is one of the main risk factors for type 2 diabetes, and peroxisome proliferator-activated receptor γ (PPARγ) is considered a promising pathway on insulin sensitivity and adipose tissue metabolism. The search for molecules acting as insulin sensitizers have increased, especially for molecules that block PPARγ-Ser273 phosphorylation, without reaching full agonism. We evaluated the effects of AM-879, a PPARγ non-agonist, and found that AM-879 exerts different effects in mice depending on the dose.
View Article and Find Full Text PDFWorldwide obesity, defined as abnormal or excessive fat accumulation that may result in different comorbidities, is considered a pandemic condition that has nearly tripled in the last 45 years. Most studies on obesity use animal models or adipocyte monolayer cell culture to investigate adipose tissue. However, besides monolayer cell culture approaches do not fully recapitulate the physiology of living organisms, there is a growing need to reduce or replace animals in research.
View Article and Find Full Text PDFThroughout the 20th and 21st centuries, the incidence of non-communicable diseases (NCDs), also known as chronic diseases, has been increasing worldwide. Changes in dietary and physical activity patterns, along with genetic conditions, are the main factors that modulate the metabolism of individuals, leading to the development of NCDs. Obesity, diabetes, metabolic associated fatty liver disease (MAFLD), and cardiovascular diseases (CVDs) are classified in this group of chronic diseases.
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