Effects of a high-fat diet on the expression of leptin and its receptor in multipotent mesenchymal cells extracted from mouse adipose tissue

• Grant number: 22/03549-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2022
• End date: December 31, 2022
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Isabel Cardoso Alonso-Vale
• Grantee: Andressa Franca de Sousa Bispo
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

A high-fat diet leads to obesity, a condition that generates important changes in white adipose tissue (WAT). Mesenchymal stem cells derived from adipose tissue (adipose derived Stromal Cells - AdSC) are responsible for generating new adipocytes, expanding adipose tissue. Changes in the expression of transcription factors and epigenetic marks in the nucleus of AdSCs may have effects on the proliferation and adipogenesis of these cells, affecting healthy expansion of WAT (hyperplastic) versus pathological expansion of WAT (hypertrophic) in obese individuals. Leptin is an adipokine with effects on the central nervous system, which include the induction of energy expenditure and satiety. Also, it has great relevance in the activation of immune cells and in the modulation of the inflammatory response. In obesity, increases in WAT accumulation and leptin levels are accompanied by hypothalamic resistance to leptin. It is known that, in obesity, the central effects of leptin are impaired, thus, its local effects may prevail and contribute to the expansion of WAT and increased inflammation. This phenomenon has been considered leptin resistance and may result from deficiencies at various levels in the leptin signaling pathway, including reduced access of the hormone to its receptor due to alterations in receptor expression or alterations in post-receptor signal transduction. Leptin-deficient ob/ob mice exhibit hypertrophy and hyperplasia of adipocytes, as well as increased WAT and systemic inflammation. WAT is a leptin-rich environment, but the local actions of leptin on adipogenesis have not been fully investigated. Thus, it is necessary to evaluate the contributions of paracrine signaling and expression of leptin and its receptors in multipotent mesenchymal cells of WAT, objective of the present project. Considering that AdSCs are progenitor cells that reside in a niche highly enriched in leptin secreted by adipocytes and macrophages in WAT in obese individuals, we hypothesized that obesity (via the action of leptin on AdSCs) would lead to important changes in epigenetic marker-promoting enzymes, which culminates in the fall in the expression of some genes commonly silenced in obesity, especially those related to adipogenesis. To study these alterations, we will evaluate the expression of leptin and its receptor by Real Time PCR, in AdSCs isolated from the subcutaneous WAT of control and obese animals (induced by a high fat diet), in order to correlate the data with other results of the group.(AU)