Table 1.

Summary of studies examining effects of manipulation of anatomically or molecularly defined neural populations on glucose metabolism and appetite

Area	Cell Type	Intervention	Effect on Metabolism	Feeding Effect	Reference
ARC	All	Overexpression of hexokinase I	Increased fasting glucose, impaired glucose tolerance	?	135
	All	Leptin injection	Increased glucose uptake into BAT	?	157
	AgRP + POMC	Leptin receptor KO	Increased insulin, normal glucose tolerance	Increased	164
	AgRP	Ribosomal S6K1 KO	Muscle insulin resistance	Normal	146
	AgRP	Postembryonic deletion	Decreased insulin	Decreased	8
	AgRP	Postembryonic deletion	Normal glucoprivic feeding	Decreased	95
	AgRP	Insulin receptor KO	Loss of insulin suppression of hepatic glucose production	Normal	85
	AgRP	AMPK2α KO	Loss of glucose sensing in subpopulation of AgRP neurons, no effect on insulin	Unchanged	25
	AgRP	Postnatal ablation by diphtheria toxin	Increased lipid utilization, decreased sympathetic outflow	Blunted refeeding	74
	AgRP	TXNIP deletion	Improved fasting glucose and glucose tolerance	Decreased weight	11
	AgRP	Glutamaterigc GluN2B receptor KO	Correction of hyperglycemia in ob/ob mice	Unchanged	162
	AgRP	Leptin receptor replacement in ob/ob mice	Correction of hyperglycemia	Normal	57
	AgRP	GHSR restoration in KO mice	Correction of hypoglycemia with calorie restriction	Normal	166
	AgRP	Carnitine acetyltransferase deletion	Reduced glucose disposal and suppression of glucose production	Decreased	129
	AgRP	CRF receptor 1 KO	Reduced hepatic glucose production in fasting in females	Normal	88
	AgRP	Loss of GABA signaling	Glucose intolerance in young mice	Reduced	106
	AgRP	Antagonism of AP1 transcription factor	Improved glucose clearance and insulin sensitivity	?	72
	POMC	Ribosomal S6K1 KO	Hepatic insulin resistance	?	146
	POMC	AMPK2α KO	Loss of glucose sensing in POMC neurons	Increased	25
	POMC	ATP-insensitive KATP channel	Impaired glucose sensing in POMC neurons, impaired glucose tolerance	?	124
	POMC	Inositol-requiring enzyme 1 deficiency	Impaired glucose and insulin tolerance, reduced hepatic insulin sensitivity	Increased	172
	POMC	Antagonism of AP1 transcription factor	Improved glucose clearance and insulin sensitivity		72
	POMC	Arcuate POMC KO	Improved glucose tolerance		22
PVH	All	MT-II injection	Increased glucose uptake into BAT	?	157
	SIM1	CB1 receptor KO	Increased insulin sensitivity on high-fat diet	Unchanged	19
DMH	All	NPY knockdown	Increased hepatic insulin sensitivity	?	93
	All	CCK receptor replacement in OLETF rats	Improved glucose homeostasis	Decreased	178
LH	All	MC4R reexpression	Improved glucose tolerance	Unchanged	111
	MCH	Insulin receptor KO	Improved glucose tolerance on high-fat diet	Normal	68
	MCH	ATP-insensitive KATP channel	Impaired glucose tolerance	Normal	83
	Orexin	Orexin KO	Loss of diurnal glucose rhythm	Unchanged	161
VMH	All	Leptin injection	Increased glucose uptake into skeletal muscle, BAT	?	157
	All	MT-II	Increased glucose uptake into skeletal muscle, BAT	?	157
	All	LIN28a viral overexpression	Improved glucose tolerance and insulin sensitivity on high-fat diet	Unchanged	79
	SF1	Leptin receptor KO	Glucose intolerance, hyperinsulinemia	Increased	9
	SF1	VGLUT KO	Hypoglycemia during fasting	?	158
	SF1	Insulin receptor KO	Protected against insulin resistance on high-fat diet	Reduced	81
	SF1	FOXO1 KO	Improved glucose tolerance and insulin sensitivity in muscle	Unchanged	80
	SF1	SOCS3 KO	Improved glucose tolerance	Reduced	174
MPO	All	Norepinephrine injection	Increased plasma glucose and insulin	?	47
VLM	CA	CA neuron ablation	Abolished hyperglycemic response to stress	?	176
PBN	CCK	Leptin receptor KO	Enhanced counterregulatory response to hypoglycemia	Unchanged	45
PAG	Leptin receptor	Optogenetic activation	Increased blood glucose	Unchanged	44

AgRP, agouti related peptide; AMPK2α, AMP-activated protein kinase α-subunit; AP1, activator protein 1; ARC, arcuate nucleus of the hypothalamus; BAT, brown adipose tissue; CA, catecholaminergic; CB1, cannabinoid type 1; CCK, cholecystokinin; CRF, corticotropin-releasing factor; DMH, dorsomedial nucleus of the hypothalamus; FOXO1, forkhead box protein O1; GABA, γ-aminobutyric acid; GHSR, growth hormone secretagogue receptor; GluN2B, glutamate ionotropic receptor NMDA type 2B; K_ATP, ATP-dependent K⁺ channel; KO, knockout; LH, lateral hypothalamus; LIN28a, RNA binding protein; MCH, melanin-concentrating hormone; MC4R, melanocortin 4 receptor; MPO, medial preoptic area; MT-II, melanotan II; NPY, neuropeptide Y; OLETF, Otsuka Long Evans Tokushima fatty rat; PAG, periaqueductal gray; PBN, parabrachial nucleus; PVH, paraventricular nucleus of the hypothalamus; POMC, proopiomelanocortin; SF1, steroidogenic factor 1; SIM-1, single-minded 1; SOCS3, suppressor of cytokine signaling 3; S6K1, ribosomal S6 protein kinase 1; TXNIP, thioredoxin-interacting protein; VGLUT, vesicular glutamate transporter; VLM, ventrolateral medulla; VMH, ventromedial hypothalamic nucleus.