Abstract:
Maternal obesity is a well-established risk factor for gestational diabetes mellitus (GDM), a condition defined by glucose intolerance with onset during pregnancy. A central mechanism underlying this association involves dysfunction of white adipose tissue (WAT), an endocrine organ that regulates energy homeostasis, inflammation, and insulin sensitivity. In healthy pregnancies, insulin resistance physiologically increases in the second and third trimesters to ensure adequate glucose supply to the fetus. This state is normally counterbalanced by enhanced pancreatic β-cell mass and insulin secretion. However, in the context of obesity, this adaptive response is compromised. In obese individuals, WAT expansion occurs predominantly through hypertrophy rather than hyperplasia, reducing its lipid storage capacity and promoting elevated circulating free fatty acids (FFAs). These FFAs accumulate in insulin-sensitive tissues such as the liver, skeletal muscle, and pancreas, exacerbating systemic insulin resistance. Moreover, dysfunctional WAT becomes a source of chronic low-grade inflammation, secreting pro-inflammatory cytokines (e.g., TNF-α, IL-6, leptin) and suppressing beneficial adipokines such as adiponectin. This altered adipokine profile directly impairs β-cell function. Reduced adiponectin levels, commonly observed in obese pregnant women, limit β-cell proliferation and survival, hindering compensation for gestational insulin demands. Concurrently, elevated FFAs and inflammatory mediators further disrupt insulin signaling and exacerbate β-cell dysfunction. Leptin excess, although typically associated with satiety, may also contribute negatively by interfering with insulin biosynthesis and secretion. Understanding how WAT dysfunction in obesity impairs β-cell adaptation is critical to elucidating GDM pathogenesis. Beyond metabolic implications, these interactions highlight the importance of achieving appropriate gestational weight gain and managing pre-existing obesity. In this session, we will explore the crosstalk between adipose tissue and pancreatic β-cells, emphasizing its relevance to maternal-fetal health and potential therapeutic targets.
