Adipogenesis

ETHNOPHARMACOLOGICAL RELEVANCE: The fruits of Terminalia bellerica Roxb. (Combretaceae) and T. chebula Retz. (Combretaceae) are important components of triphala, a popular Ayurvedic formulation, for treating diabetes in Indian traditional medicine. AIM OF THE STUDY: The aim of this study was to evaluate the effects of the constituents of T. bellerica and T. chebula fruit extracts on PPAR? and PPAR? signaling/expression, cellular glucose uptake and adipogenesis. MATERIALS AND METHODS: PPAR? and PPAR?

Medicinal plants are a rich source of ligands for nuclear receptors. The present study was aimed to screen a collection of plant extracts for PPAR?/?-activating properties and identify the active extract that can stimulate cellular glucose uptake without enhancing the adipogenesis. A reporter gene assay was performed to screen ethanolic extracts of 263 plant species, belonging to 94 families, for activation of PPAR? and PPAR?. Eight extracts showed activation of PPAR?, while 22 extracts showed activation of PPAR?.

The thiazolidinedione (TZDs) class of drugs are very effective for the treatment of type 2 diabetes mellitus (T2DM). But due to the adverse effects of synthetic TZDs, their use is strictly regulated. The therapeutic actions of TZDs are mediated via modulation of peroxisome proliferator-activated receptor gamma (PPAR?). Naturally occurring PPAR? modulators are more desirable as they lack the serious adverse effects caused by TZDs. This has prompted the exploitation of medicinal plants used in traditional medicine, for their potential PPAR? activity.

Psychotropic agents are notorious for their ability to increase fat mass in psychiatric patients. The two determinants of fat mass are the production of newly differentiated adipocytes (adipogenesis), and the volume of lipid accumulation. Epigenetic programs have a prominent role in cell fate commitments and differentiation required for adipogenesis. In parallel, epigenetic effects on energy metabolism are well supported by several genetic models.

Adipocytes are insulin sensitive cells that play a major role in energy homeostasis. Obesity is the primary disease of fat cells and a major risk factor for the development of Type II diabetes, cardiovascular disease, and metabolic syndrome. Obesity and its related disorders result in dysregulation of the mechanisms that control adipocyte gene expression and function. To identify potential novel therapeutic modulators of adipocytes, we screened 425 botanical extracts for their ability to modulate adipogenesis and insulin sensitivity.

G(s)alpha, the G protein that mediates receptor-stimulated cAMP generation, has been implicated as a regulator of adipogenesis and adipose tissue function. Heterozygous G(s)alpha mutations lead to obesity in Albright hereditary osteodystrophy (AHO) patients and in mice. In this study, we generated mice with adipose-specific G(s)alpha deficiency. Heterozygotes had 50% loss of G(s)alpha expression in adipose tissue and no obvious phenotype, suggesting that adipose-specific G(s)alpha deficiency is not the cause of obesity in AHO.

Conjugated linoleic acid (CLA) supplementation decreases adipose mass and increases bone mass in mice. Recent clinical studies demonstrate a beneficial effect of CLA on reducing weight and adipose mass in humans. This article reviews possible biological mechanisms of action of CLA on bone metabolism, focusing on modulation of nuclear receptor peroxisome proliferator-activated receptor gamma activity to steer mesenchymal stem cell differentiation toward an adipose and away from an osteoblast lineage.

AMP-activated protein kinase (AMPK) is a sensor and regulator of cellular energy metabolism potentially implicated in a broad range of conditions, including obesity and Alzheimer's disease. Its role in the control of key metabolic enzymes makes this kinase a central player in glucose and lipid homeostasis.

The bone undergoes continuous remodeling of osteoblastic bone formation and osteoclastic bone resorption to maintain proper bone mass. It is also reported that bone marrow adiposity has a reciprocal role in osteoblasts due to their same origin from mesenchymal stem cells. In addition, one of the key mediators of adipogenesis, peroxisome-proliferator activated receptor-γ (PPARγ), plays a significant role in osteoblastogenesis in bone marrow mesenchymal stem cells. One dietary component that is known to have significant impact on adiposity and bone mass is conjugated linoleic acid (CLA).

BACKGROUND: Many breast cancer patients are plagued by the disabling complication of upper limb lymphedema after axillary surgery. Conservative treatments using massage and compression therapy do not offer a lasting relief, as they fail to address the chronic transformation of edema into excess adipose tissue. Liposuction to address the adipose nature of the lymphedema has provided an opportunity for a detailed analysis of the stromal fraction of lymphedema-associated fat to clarify the molecular mechanisms for this adipogenic transformation.