Activation of PPARγ at an Early Stage of Differentiation Enhances Adipocyte Differentiation of MEFs Derived from Type II Diabetic TSOD Mice and Alters Lipid Droplet Morphology

Abstract

Type 2 diabetic Tsumura, Suzuki, obese, diabetes (TSOD) mice gradually gain weight as compared to corresponding Tsumura, Suzuki, non-obesity (TSNO) control mice, and develop insulin resistance. Although development of type 2 diabetes mellitus is associated with dysfunction of adipocytes, little is known about the properties of adipocytes from TSOD mice. Therefore, we attempted to remove intracorporeal factors and elucidate inherent properties of adipocytes of TSOD mice using adipocytes differentiated from mouse embryonic fibroblasts ( Key words adipocyte; differentiation; obesity; peroxisome proliferator-activated receptor-γ (PPARγ); rosiglitazone; Tsumura, Suzuki, obese, diabetes (TSOD) mouseThe worldwide population with type 2 diabetes mellitus (T2DM) is increasing, and the number of patients reached 415 million in 2015.1) Since T2DM is associated with vascular and other end-organ disease, 2) prevention of T2DM is a major public health issue. It is well known that obesity is a major risk factor for T2DM.3) Notably, incident of T2DM is correlated with abdominal visceral adipose tissue mass in humans.4) Therefore, understanding of roles of adipose tissue in the development of T2DM may lead to better methods for prevention of T2DM.Adipose tissue plays important roles in energy storage and release, and secretes various cytokines. Previous studies show that adipose-specific knockout of mitochondrial transcription factor A enhances energy expenditure and protects from dietinduced obesity and insulin resistance in mice.5) Moreover, adipose-specific glucose transporter type 4 (GLUT4) knockout mice exhibit insulin resistance and diabetes via secretion of retinol binding protein-4. 6) Thus, adipose functions are closely associated with the development of insulin resistance and T2DM. However, since T2DM is a complex illness resulting from a variety of genetic and environmental factors, single gene knockout mice provide limited information on the roles of adipose tissue in the development of T2DM. Therefore, more suitable model of human T2DM have been needed for such a kind of research.In 1992, the Tsumura, Suzuki, obese, diabetes (TSOD) mouse has been established as an animal model of human T2DM by the selective breeding of male mice of ddY strain with heavy body and urinary glucose.7) The mice exhibit overeating and gradually gain weight as compared to corresponding control mice, Tsumura, Suzuki, non-obesity (TSNO), and high blood glucose and urinary glucose are frequently observed in male mice of TSOD. Quantitative trait locus (QTL) analysis reveal that body weight and blood glucose levels in male mice of TSOD are affected by combination of multiple genetic loci (e.g., NIDD4,5,6).8) Several studies examine the roles of adipose tissue in development of T2DM using the mice and show that insulin-dependent glucose uptake 9) and GLUT4 translocation to the plasma membrane 10) is impaired in the adipose tissue. However, since these properties may be developed by various intracorporeal factors such as hormones and cytokines, t...

Involvement of mechano-sensitive Piezo1 channel in the differentiation of brown adipocytes

“…It is reported that Pparγ is expressed in early stage of differentiation in adipocyte [ 36 , 37 ]. In addition, PPARγ activation during early-stage differentiation enhanced the differentiation of 3T3-L1 cells into white adipocytes [ 38 , 39 ] and PPARγ activation during early-stage differentiation into white adipocytes was also enhanced in an embryonic fibroblast model of type 2 diabetes [ 40 ]. Those reports and our results suggest that Piezo1 suppresses differentiation by inhibiting Pparγ expression via the calcineurin pathway during the induction and early stage of differentiation.…”

Gestational diabetes mellitus is associated with decreased adipose and placenta peroxisome proliferator-activator receptor γ expression in a Chinese population

“…However, it would be helpful for us to have a better understanding of the PPARγ underlying the pathophysiology of GDM if more clinical samples can be collected from pregnant women for examination. As PPARγ is involved in glucose and lipid metabolism in type 2 diabetes mellitus [ 24 , 25 ], it is probable that PPARγ may also play important roles in the GDM. In the present study, decreased expression of PPARγ was observed in both adipose tissues and placenta tissues from patients with GDM.…”

Beyond energy provider: multifunction of lipid droplets in embryonic development

“…PPARα, in particular, is a significant nuclear receptor that controls the expression of the CPT1 gene, which is involved in FA catabolism [ 87 ]. The activity of PPARγ affects the formation of LDs in adipocytes [ 88 ]. Long-chain lipid CoA synthase is a key player in body lipid metabolism and is associated with various diseases.…”