Leptin decreases gluconeogenesis and gluconeogenic substrate availability in patients with lipodystrophy.

Metreleptin treatment in patients with lipodystrophy reduced GNG likely through decreased availability of carbon sources for gluconeogenesis, such as alanine, lactate, and glycerol. Associations between alanine and GNG persisted after metreleptin treatment while correlations with glycerol and palmitate Ra did not persist, suggesting reduced importance of lipolysis as a driver of GNG in the leptin-replete state.