Preproghrelin expression is a key target for insulin action on adipogenesis

Area of Science:

• * Molecular Endocrinology
• * Cellular Biology
• * Metabolic Research

Background:

• * Adipogenesis, the process of fat cell differentiation, is critical for energy homeostasis.
• * The role of preproghrelin and its derived peptides in regulating adipogenesis remains incompletely understood.
• * Ghrelin signaling pathways are implicated in metabolic regulation, but their specific contribution to adipogenesis requires further elucidation.

Purpose of the Study:

• * To investigate the function of preproghrelin-derived peptides in the process of adipogenesis.
• * To identify key molecular regulators and signaling pathways involved in preproghrelin-mediated adipogenesis.
• * To explore the potential autocrine/paracrine roles of these peptides in white adipose tissue.

Main Methods:

• * Immunocytochemistry was used to analyze preproghrelin expression in 3T3-L1 adipocytes and preadipocytes.
• * Preproghrelin knockdown experiments and antibody neutralization of specific peptides (acylated ghrelin, unacylated ghrelin, obestatin) were performed.
• * Expression levels of ghrelin-associated enzymes (PC1/3, MBOAT4) and receptors (GHSR1a, GPR39) were assessed during adipogenesis.

Main Results:

• * Preproghrelin expression was upregulated during adipogenesis, promoted by insulin, with mTORC1 as a key downstream target.
• * Preproghrelin knockdown impaired adipogenesis, while neutralization of specific peptides supported their adipogenic potential.
• * Expression of PC1/3 and MBOAT4, along with receptors GHSR1a and GPR39, was observed during adipogenesis, suggesting autocrine/paracrine signaling.

Conclusions:

• * Preproghrelin-derived peptides play a significant role in promoting adipogenesis.
• * Insulin and mTORC1 signaling are critical regulators of preproghrelin expression during adipogenesis.
• * Autocrine/paracrine mechanisms involving ghrelin peptides and their receptors are involved in regulating fat cell formation.