Metformin Inhibits Lipid Droplets Fusion and Growth via Reduction in Cidec and Its Regulatory Factors in Rat Adipose-Derived Stem Cells.

Metformin is still being investigated due to its potential use as a therapeutic agent for managing overweight or obesity. However, the underlying mechanisms are not fully understood. Inhibiting the adipogenesis of adipocyte precursors may be a new therapeutic opportunity for obesity treatments. It is still not fully elucidated whether adipogenesis is also involved in the weight loss mechanisms by metformin. We therefore used adipose-derived stem cells (ADSCs) from inguinal and epididymal fat pads to investigate the effects and mechanisms of metformin on adipogenesis in vitro. Our results demonstrate the similar effect of metformin inhibition on lipid accumulation, lipid droplets fusion, and growth in adipose-derived stem cells from epididymal fat pads (Epi-ADSCs) and adipose-derived stem cells from inguinal fat pads (Ing-ADSCs) cultures. We identified that cell death-inducing DFFA-like effector c (Cidec), Perilipin1, and ras-related protein 8a (Rab8a) expression increased ADSCs differentiation. In addition, we found that metformin inhibits lipid droplets fusion and growth by decreasing the expression of Cidec, Perilipin1, and Rab8a. Activation of AMPK pathway signaling in part involves metformin inhibition on Cidec, Perilipin1, and Rab8a expression. Collectively, our study reveals that metformin inhibits lipid storage, fusion, and growth of lipid droplets via reduction in Cidec and its regulatory factors in ADSCs cultures. Our study supports the development of clinical trials on metformin-based therapy for patients with overweight and obesity.

Three-dimensional molar enamel thickness and distribution patterns in Late Miocene Lufengpithecus lufengensis from Shihuiba, Southwest China.

Enamel thickness and distribution provide dietary insights in hominoids. Yet, three-dimensional (3D) enamel analysis of the Late Miocene Lufengpithecus from southwest China is lacking. We digitally reconstructed 68 unworn or lightly worn Lufengpithecus (L.) lufengensis molars using micro-computed tomography (micro-CT). Comparisons with modern humans, Homo erectus, extant/fossil Pongo, Pan, and Gorilla reveal L. lufengensis has "intermediate/thick" enamel, thicker than Pongo and Gorilla, but thinner than modern humans and H. erectus. In enamel distribution, relatively thicker enamel lies on the lingual cusps of the maxillary molars. The hypoconid, hypoconulid, and entoconid exhibit relatively thicker enamel compared to the metaconid and protoconid of the mandibular molars. L. lufengensis also exhibits an uneven pattern on the lingual and buccal walls. With relatively intermediate/thick enamel and distinctive distribution pattern, L. lufengensis may be able to respond to dietary variation in seasonal habitats.

Flipped classroom assisted by Rain Classroom for anatomy practical classes: Challenges and opportunities of anatomy education.

Anatomy practical classes are an essential part of learning human anatomy. The flipped classroom teaching model has been used in medical education in recent years. However, its precise impacts on anatomical knowledge acquisition and learning outcomes remain controversial. With the development of information technology, new educational tools, such as Rain Classroom, have recently attracted much interest. The Rain Classroom is an application that can easily connect students and teachers through smartphones or computers. However, whether and how to apply it to the flipped classroom in anatomy practical classes needs to be evaluated. In this study, we designed a teaching model of flipped classroom assisted by Rain Classroom and carried it out in anatomy practical classes at our university. Results showed that the final exam scores of the experimental group were significantly improved, compared with the control group (p < 0.01); the final exam score was significantly correlated with both the pre-class quiz score (p < 0.05) and the in-class quiz score (p < 0.001). Student satisfaction was measured by a questionnaire on a Likert scale of 1-5. All the mean scores were greater than 4.5, indicating that most students had positive attitudes toward this teaching model. The present study suggests that the Rain Classroom helps support students throughout the learning processes of the flipped classroom, and the model of flipped classroom assisted by Rain Classroom could improve students' learning efficiency and ultimately increase their exam performance in anatomy practical classes.

Ups and downs: The PPARγ/p-PPARγ seesaw of follistatin-like 1 and integrin receptor signaling in adipogenesis.

OBJECTIVE: Although Follistatin-like protein 1 (FSTL1), as an "adipokine", is highly expressed in preadipocytes, the detail role of FSTL1 in adipogenesis and obesity remains not fully understood. METHODS: In vitro differentiation of both Fstl1-/- murine embryonic fibroblasts (MEFs) and stromal vascular fraction (SVF) were measured to assess the specific role of FSTL1 in adipose differentiation. Fstl1 adipocyte-specific knockout mice were generated to evaluate its role in obesity development. Gene expression analysis and phosphorylation patterns were performed to check out the molecular mechanism of the biological function of FSTL1. RESULTS: FSTL1 deficiency inhibited preadipocytes differentiation in vitro and obesity development in vivo. Glycosylation at N142 site was pivotal for the biological effect of FSTL1 during adipogenesis; the conversion between PPARγ and p-PPARγ was the key factor for the function of FSTL1. Molecular mechanism studies showed that FSTL1 functions through the integrin/FAK/ERK signaling pathway. CONCLUSIONS: Our results suggest that FSTL1 promotes adipogenesis by inhibiting the conversion of PPARγ to p-PPARγ through the integrin/FAK/ERK signaling pathway. Glycosylated modification at N142 of FSTL1 is the key site to exert its biological effect.