Table 1.

Metabolic phenotypes in mice with tissue-specific deletion of leptin signaling molecules

Protein	Pathway(s)	Targeted Cells	Cre Used	Leptin Sensitivity	Food Intake	Energy Expenditure	Susceptibility to DIO	Ref No.
LEPR	All	Whole body		↓	↑↑↑	↓↓↓	ND	192
		Brain	Synapsin I	↓	ND	ND	ND	36
		AgRP neurons	AgRP	ND	↔	↓	ND	200
		POMC neurons	POMC	ND	↔	↔	ND	3, 200
		AgRP and POMC neurons	AgRP and POMC	↓	↔	↓	ND	200
		VMH neurons	SF-1	ND	↔	↔	↑	13
SH2B1	JAK2/STAT3	Whole body		↓	↑	↑	ND	120, 166
	IRS/PI 3-kinase
STAT3	JAK2/STAT3	Brain	Nestin	↓	↑↑↑	↓↓↓	ND	64
		Hypothalamus	RIP	↓	↑↑	ND	ND	40
		LEPR neurons	LEPRb	ND	↑↑↑	ND	ND	161
		POMC neurons	POMC	↔	↑	ND	↔	214
		AgRP neurons	AgRP	↓	↔	↔	↔	69
STAT5	JAK2/STAT5	Brain	Nestin	ND	↑	↓	ND	114
IRS2	IRS/PI 3-kinase	Whole body		↓	↑↑	ND	ND	24
		Brain	Nestin	↔	↑↑	↓	ND	32, 187
		Hypothalamus	RIP	↔ or ↓	↑↑	ND	ND	32, 110, 122
		POMC neurons	POMC	↔	↔	ND	ND	32
p85α/β	IRS/PI 3-kinase	POMC neurons	POMC	↓	↔	↔	ND	82
PDK1	IRS/PI 3-kinase	POMC neurons	POMC	ND	↑	ND	↑	8
PTEN	IRS/PI 3-kinase	LEPR neurons	LEPRb	ND	↔	↑	ND	163
		POMC neurons	POMC	ND	↑	↔	↑	162
FOXO1	IRS/PI 3-kinase	Whole body		↑	ND	ND	ND	105
TSC1	mTOR/S6K	Hypothalamus	RIP	↓	↑↑	ND	ND	141
		POMC neurons	POMC	↓	↑↑	ND	ND	141
SHP2	SHP2/MAPK	Brain	CaMKIIa	↓	↔	ND	ND	221
AMPKα2	AMPK/ACC	POMC neurons	POMC	↔	↑	↓	↑	34
		AgRP neurons	AgRP	ND	↔	↔	↔	34
CaMKK2	AMPK/ACC	Whole body		ND	↓	ND	↓	1
SOCS3	All	Whole body		↑	↔	ND	↓	86
		Brain	Nestin	↑	↓	ND	↓	140
		Brain	Synapsin I	↑	↓	ND	↓	140
		POMC neurons	POMC	↑	↔	ND	↓	101
		VMH neurons	SF-1	↑	↓	↓	↔	222
PTP1B	All	Brain	Nestin	↑	↓	↑	↓	11

LEPR, leptin receptor; LEPRb, long form of the leptin receptor; AgRP, agouti-related protein; POMC, proopriomelanocortin; VMH, ventromedial hypothalamus; IRS, insulin receptor substrate; PI, phosphoinositide; PDK1, phosphoinositide-dependent protein kinase-1; PTEN, phosphatase and tensin homolog deleted on chromosome 10; FOXO1, forkhead box O1; TSC1, tuberous sclerosis complex 1; mTOR, mammalian target of rapamycin; SHP2, SH2-containing protein tyrosine phosphatase 2; AMPK, AMP-activated protein kinase; ACC, acetyl-CoA carboxylase; SOCS3, suppressor of cytokine signaling-3; PTP1B, protein tyrosine phosphatase 1B; ↑increased; ↓decreased; ↔no change compared with control mice; ND, not determined; DIO, diet-induced obesity; RIP, rat insulin II promoter; SF-1, steroidogenic factor-1.