Endocrine Abstracts

NESFATIN-1 is a recently identified hypothalamic satiety molecule derived from its precursor protein, NEFA/nucleobindin2 (NUCB2). Although the hypothalamus is considered the cornerstone for maintenance of energy homeostasis, adipose tissue plays an important role in the integration of metabolic activity and energy balance; communicating with peripheral organs and the brain via secreted proteins, termed adipokines. Many hypothalamic satiety regulatory peptides have been described to be produced by adipose tissue. We therefore investigated whether Nesfatin-1/NUCB2 is produced by the adipose tissue.

Both qRT-PCR and Western blot analysis revealed that Nesfatin-1/NUCB2 is highly expressed in both human and rodent adipose tissue; immunohistochemical analysis revealed intense cytoplasmic staining for nesfatin-1. Subcutaneous (SC) adipose tissue expression of Nesfatin-1 was shown to be significantly higher in comparison to the omental depot. Moreover, higher levels of Nesfatin-1 were detected in adipose tissue of murine models of obesity, namely ob/ob and db/db mice as well as high-fat fed mice, compared to controls.

Interestingly, food depravation reduced nesfatin-1 levels in subcutaneous tissue whilst increasing its expression in omental tissue. Stimulation of SC adipose tissue explants for 24 h with inflammatory cytokines (TNFα and IL-6), insulin and dexamethasone, all elevated in obese individuals, resulted in a marked increase in nesfatin levels. Furthermore, we present robust evidence that the secretion of Nesfatin-1/NUCB2 into the culture media was dramatically increased during the differentiation of 3T3-L1 cells preadipocytes into adipocytes.

These data demonstrate that Nesfatin-1/NUCB2 is a novel adipokine, whose expression is significantly higher in obesity and is altered in states of food deprivation.