Table 3.

Effects of inflammation-related signaling mediators on energy balance and body weight

	Gene	Models	Site applied	Food intake	Energy expenditure	Body weight	Neuropeptide mRNA	Ref
Proinflammatory cytokines	Tumor necrosis factor-α (TNF-α)	KO	Whole body	↓		Anti-obesity		156,157
		icv injection (low-dose)	Brain	↑	↓		Pomc↓, TRH↓, CRH↓	82,155
		icv injection (high-dose)	Brain	↓	↑		Pomc↑, Agrp↓	82,312
	TNF-α receptor 1 (TNFR1)	KO	Whole body	↑	↑	Anti-obesity	Pomc↓, Agrp↑, TRH↑	155,158
	Interleukin-1 (IL-1)	KO	Whole body			Mature-onset obesity		164
		icv injection (high-dose)	Brain	↓	↑	↓		83,84,313,314
	Interleukin-1 receptor I (IL-1RI)	KO	Whole body	↑	↓	Mature-onset obesity		165
	IL-1 receptor antagonist (IL-1Ra)	KO	Whole body	↓ or no change	↑ or no change	↓	No changes	341,342
	Interleukin-6 (IL-6)	KO	Whole body	↑		Mature-onset obesity		166
		icv injection (high-dose) or overexpression	Brain	↓	↑	↓	Pomc↑, Npy↓, Agrp↓	85,166, 169
	Interleukin-18 (IL-18)	KO	Whole body	↑	↓	Mature-onset obesity	No changes	86,315
		icv injection (high-dose)	Brain	↓		↓		86
	Leukemia inhibitory factor (LIF)	icv injection or overexpression	Brain	↓	No change	↓		87,168
	Brain-derived neurotrophic factor (BDNF)	KO (+/−)	Whole body	↑	↑	↑	No changes	167
		icv injection (high-dose)	Brain	↓	↑	↓	Pomc↑, Agrp↑, TRH↑	88,316
	Ciliary neurotrophic factor (CNTF)	icv injection (high-dose)	Brain	↓		↓	Npy↓	89,317
	GM-CSF	KO	Whole body		↓	Mature-onset obesity	No changes	90
		icv injection (high-dose)	Brain	↓		↓	Npy↓, Agrp↓
	Resistin	KO (+/−)	Whole body		↓	↑		363
		icv injection (high-dose)	Brain	↓		↓	CART↑, Npy↓ or ↑, Agrp↓	163,318
Proinflammatory factors	X box binding protein 1 (XBP1)	KO	Brain	↑	↓	↑	Npy↑, Agrp↑	74
	IKKβ	KO	Brain	↓		Anti-obesity		66
	c-Jun N-terminal kinase 1 (JNK1)	KO	Whole body			Anti-obesity		181
		KO	Brain	↓	↑	Anti-obesity	Agrp↑	75,76,187
	Toll-like receptor 2 (TLR2)	KO	Whole body			Anti-obesity		153
	Toll-like receptor 4 (TLR4)	KO	Whole body					149
	MyD88	KO	Brain	↓	↑	Anti-obesity		68
	PTP1B	KO	Whole body		↑	Anti-obesity		204,205
		KO	Brain		↑	Anti-obesity		207
	SOCS3	KO (+/−)	Whole body	↓		Anti-obesity	Npy↓, Agrp↓	198
		KO	Brain	↓		Anti-obesity	leptin-induced Pomc↑	199
		KO	POMC neuron	↓	↑	Anti-obesity	Pomc↑, Npy↓	77
		KO	SF1 neuron	↓	↓	No change		79
	α-lipoic acid	icv injection	Brain	↓	↑	Anti-obesity		226
	AMPK 2α	KO	AGRP neuron	↓	No change	↓		225
			POMC neuron	↑	↓	↑
	TSC1 (mTOR inhibitor)	KO	POMC	↑		↑	Pomc↓, Npy↑	237
	Sirtuin 1 (SIRT1)	Chemical inhibitor or siRHA	Brain or arcuate	↓		↓	Pomc↑, Agrp↓	251
		KO	AGRP neuron	↓	No change	↓		252
		KO	POMC neuron		↓	↑		249
		KO	SF1 neuron		↓	↑		250
	Sirtuin 3 (SIRT3)	KO	Whole body		↓	↑		256
	Sirtuin 6 (SIRT6)	KO	Brain			↑	Pomc↓	255
	Lipoprotein receptor LRP1	KO	Brain	↑	↓	↑	Npy↑, Agrp↑	335
	Lipoprotein lipase (LPL)	KO	Brain	↑	↓	↑	Npy↑, Agrp↑	336
	Fatty acid synthase (FAS)	KO	via RIP Cre	↓	↑	↓		334
	Long-chain fatty acyl-CoA	icv injection	Brain	↓		↓	Npy↓, Agrp↓	333

“High-dose” reflects the injected doses in ng or μg, while “low-dose” reflects the injected doses in pg. Abbreviations: KO, knockout; icv, intracerebroventricular; ↓ decrease; ↑ increase.