Table 2.

Evidence for direct promotor binding and transcriptional activity of leptin signalling molecules on target genes relevant to metabolic and reproductive function. See Figure 1 legend for abbreviations of signalling molecules.

Signalling Pathway	Target Gene	Description of Findings	Reference
STAT3	Npy	Leptin actions via the 221-bp region of the Npy promotor, which possesses two putative STAT3 binding sites.	[124]
	Agrp	STAT binding sites upstream of Agrp (but not STAT3 itself) are required for fasting-induced Agrp transcription.	[124,125]
	Pomc	Leptin and STAT3 increased Pomc promoter activity. A 30-bp promoter element is required for leptin regulation.	[58,126]
	TRH	STAT3-response elements identified in Trh promoter.	[127]
	Socs3	STAT3-bindis to the Socs3 promoter.	[127]
	ERα	ERα promoter contains a STAT3 response element.	[85]
FOX01 and STAT3	Agrp and Pomc	Leptin-induced phospho-STAT3 activates the POMC promoter via an SP1-binding site which overlaps with a FOX01-binding element. FOXO1 binds to STAT3 and prevents it from interacting with the promoter. FOXO1 and STAT3 exert opposing actions on Agrp and Pomc expression. FOXO1 activates Agrp and inhibitis Pomc.	[56,57,58]
FOX01	NPY, AGRP and Pomc	FOXO1 binds upstream of the NPY coding region and increases NPY promoter activity. Foxo1-mediated NPY transcription is negatively regulated by leptin, insulin and PI3K/Akt signalling. Foxo1 increases AGRP promoter activity but not Pomc promoter activity.	[58]
AMPK-CRTC1	Cartpt and Kiss1	Cartpt and Kiss1 promoters contain CREB binding sites. Leptin recruits CRTC1 to Cart and Kiss1 promoters.	[37]