Sex- and depot-specific differences in cellular insulin responsiveness during adipose expansion.

Background: Adipose tissue distribution, metabolism, and expansion capacity exhibit notable sex- and depot-specific differences. Herein, we monitored adipocyte traits related to insulin responsiveness and glucose transport during adipose expansion in visceral and subcutaneous fat from male and female mice.

Materials And Methods: Adipocytes were isolated from perigonadal and inguinal adipose tissue of chow-fed female and male C57Bl6/J mice and assessed for adipocyte size distribution using a coulter counter; glucose uptake and cytosolic volume were measured using glucose tracer assays.

Focal Adhesion Kinase Orchestrates GLUT4 Translocation and Glucose Uptake via Cytoskeletal Turnover in Primary Adipocytes.

Intact insulin signaling and glucose transport in adipocytes are crucial to maintaining whole-body energy metabolism. Focal adhesion kinase stands as a central intracellular protein facilitating signaling between the extracellular matrix and the cytoplasm, thereby regulating cellular metabolism. Here, we have investigated the role of focal adhesion kinase in adipocyte glucose transport using an array of methods, including affinity purification combined with quantitative mass spectrometry, glucose tracer assays, western blotting, and confocal imaging.

Adipocyte traits limiting cellular insulin responsiveness and glucose transport.

Adipocyte dysfunction is a hallmark of systemic insulin resistance. Insulin-responsive glucose transporter 4 (GLUT4) is downregulated in the insulin resistant state, and cellular insulin responsiveness varies depending on fat depot origin and degree of adipose expansion. Here, we have resolved factors limiting cellular insulin responsiveness, by examining adipocyte function and traits related to glucose transport at the cellular level.

EHD2 regulates plasma membrane integrity and downstream insulin receptor signaling events.

Adipocyte dysfunction is a crucial driver of insulin resistance and type 2 diabetes. We identified EH domain-containing protein 2 (EHD2) as one of the most highly upregulated genes at the early stage of adipose-tissue expansion. EHD2 is a dynamin-related ATPase influencing several cellular processes, including membrane recycling, caveolae dynamics, and lipid metabolism.

Expansion of the Inguinal Adipose Tissue Depot Correlates With Systemic Insulin Resistance in C57BL/6J Mice.

To accommodate surplus energy, the adipose tissue expands by increasing adipocyte size (hypertrophy) and number (hyperplasia). The presence of hypertrophic adipocytes is a key characteristic of adipose tissue dysfunction. High-fat diet (HFD) fed C57BL/6J mice are a commonly used model to study obesity and obesity-related complications.

Rosiglitazone treatment enhances intracellular actin dynamics and glucose transport in hypertrophic adipocytes.

Aims: To accommodate surplus energy, adipose tissue expands by increasing both adipose cell size (hypertrophy) and cell number (hyperplasia). Enlarged, hypertrophic adipocytes are known to have reduced insulin response and impaired glucose transport, which negatively influence whole-body glucose homeostasis. Rosiglitazone is a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, known to stimulate hyperplasia and to efficiently improve insulin sensitivity.