The Effects of Obesity on Outcome in Preclinical Animal Models of Infection and Sepsis: A Systematic Review and Meta-Analysis

Table 1

Study characteristics.

Study (author, year)	Exp #	Species	Age (wk)	Sex	Obesity model		Challenge				Observation period
					Type	GT/DC	Type	Strain	Route	Dose
Single-strain bacteria models
Hsu, 2007	1	Mouse	8–12	F	Gen	ob/ob	S. pneumoniae	n/a	IT	10^5 CFU	10 d
	2	Mouse	8–12	M	Gen	ob/ob/lep	S. pneumoniae	n/a	IT	10^5 CFU	10 d
Strandberg, 2009	3	Mouse	5–7	M	Gen	ob/ob	S. aureus	n/a	IV	5 × 10^7 CFU	17 d
	4	Mouse	5–7	M	DIO	HFD	S. aureus	n/a	IV	5 × 10^7 CFU	17 d
Mancuso, 2014	5	Mouse	16–18	F	Gen	CPE^F/F	S. pneumoniae	n/a	IT	5 × 10^4 CFU	10 d
Svahn, 2015	6	Mouse	6	M	DIO	HFDP	S. aureus	n/a	IV	3.8–4.5 × 10^7 CFU	17 d
	7	Mouse	6	M	DIO	HFDS	S. aureus	n/a	IV	3.8–4.5 × 10^7 CFU	17 d
	8	Mouse	6	M	DIO	HFDS-HP	S. aureus	n/a	IV	3.8–4.5 × 10^7 CFU	17 d
	9	Mouse	6	M	DIO	HFDS-LP	S. aureus	n/a	IV	3.8–4.5 × 10^7 CFU	17 d
Svahn, 2016	10	Mouse	6	M	DIO	HFDS	S. aureus	n/a	IV	3–5.4 × 10^7 CFU	17 d
	11	Mouse	6	M	DIO	HFDw6	S. aureus	n/a	IV	3–5.4 × 10^7 CFU	17 d
Wan, 2016	12	Mouse	3-4	M	DIO	HFD	E. coli	n/a	IN	10^9 CFU	96 h
	13	Mouse	3-4	M	DIO	HFD	E. coli	n/a	IN	10^10 CFU	96 h
Cecal ligation and puncture models
Tschop, 2010	14	Mouse	6–10	M	Gen	ob/ob	Polymicrobial	n/a	IP	n/a	240 h
	15	Mouse	6–10	M	DIO	HFD	Polymicrobial	n/a	IP	n/a	240 h
	16	Mouse	6–10	M	Gen	ob/ob	Polymicrobial	n/a	IP	n/a	240 h
Kaplan, 2012	17	Mouse	6	M	DIO	HFD	Polymicrobial	n/a	IP	n/a	30 h
Siegl, 2014	18	Mouse	19	M	DIO	HFD	Polymicrobial	n/a	IP	n/a	240 h
Kaplan, 2016	19	Mouse	6	M	DIO	HFD	Polymicrobial	n/a	IP	n/a	48 h
Lipopolysaccharide
Fagioni, 1998	20	Mouse	5	F	Gen	ob/ob	E. coli 055:B5	n/a	IP	30 μg	7 d
	21	Mouse	5	F	Gen	ob/ob	E. coli 055:B5	n/a	IP	100 μg	7 d
	22	Mouse	5	F	Gen	ob/ob	E. coli 055:B5	n/a	IP	300 μg	7 d
	23	Mouse	5	F	Gen	db/db	E. coli 055:B5	n/a	IP	30 μg	7 d
	24	Mouse	5	F	Gen	db/db	E. coli 055:B5	n/a	IP	100 μg	7 d
	25	Mouse	5	F	Gen	db/db	E. coli 055:B5	n/a	IP	300 μg	7 d
Segersvard, 2003	26	Rat	NR	M	DIO	HFD35	E. coli	n/a	IP	2 mg	72 h
	27	Rat	NR	M	DIO	HFD60	E. coli	n/a	IP	2 mg	72 h
Suto, 2007	28	Mouse	NR	F	Gen	B6AY12w	E. coli 0111-B4	n/a	IP	50 μg	7 d
	29	Mouse	NR	F	Gen	B6Ay12w	E. coli 0111-B4	n/a	IP	100 μg	7 d
	30	Mouse	NR	F	Gen	B6-ob/ob	E. coli 0111-B4	n/a	IP	100 μg	7 d
	31	Mouse	NR	F	Gen	B6Ay12w	E. coli 0111-B4	n/a	IP	200 μg	7 d
	32	Mouse	NR	F	Gen	B6Ay10m	E. coli 0111-B4	n/a	IP	50 μg	7 d
	33	Mouse	NR	F	Gen	B6Ay10m	E. coli 0111-B4	n/a	IP	100 μg	7 d
Sakai, 2013	34	Rat	4	M	DIO	HFD	E. coli 0111-B4	n/a	IP	10 mg/kg	24 h
Fujiwara, 2014	35	Rat	4	M	DIO	HFD	E. coli 0111-B4	n/a	IP	10 mg/kg	12 h
	36	Rat	4	M	DIO	HFD	E. coli 0111-B4	n/a	IP	10 mg/kg	12 h
Single-strain virus models
Smith, 2007	37	Mouse	NR	NR	DIO	HFD	H1N1 influenza A	A/PR8	IN	2 HG units	10 d
Easterbrook, 2011	38	Mouse	20	M	DIO	HFD	H1N1 influenza A	CA/09	IN	2.5 × 10^5 pfu	15 d
	39	Mouse	20	M	DIO	HFD	H1N1 influenza A	NY312	IN	2.5 × 10^5 pfu	15 d
	40	Mouse	20	M	DIO	HFD	H1N1 influenza A	Sw31	IN	50ul-SW31	15 d
Milner, 2013	41	Mouse	NR	M	DIO	HFD-UP	H1N1 influenza A	A/PR8	PO	5.3 × 10^5 TCID50	13 d
	42	Mouse	NR	M	DIO	HFD-P	H1N1 influenza A	A/PR8	PO	5.3 × 10^5TCID50	13 d
Radigan, 2014	43	Mouse	8–12	NR	Gen	db/db	H1N1 influenza A	A/WSN/33	IT	500 pu	14 d
	44	Mouse	8–12	NR	Gen	db/db	H1N1 influenza A	A/WSN/33	IT	1500 pu	14 d
O’Brien, 2015	45	Mouse	11	M	DIO	HFD	H1N1 influenza A	CA/09	IN	1 × 10^5 TCID50	10 d
	46	Mouse	8	M	Gen	ob/ob	H1N1 influenza A	CA/09	IN	1 × 10^5 TCID50	10 d
	47	Mouse	11	M	DIO	HFD	H3N2 influenza A	HK68	IN	6.3 × 10^5 TCID50	10 d
	48	Mouse	8	M	Gen	ob/ob	H3N2 influenza A	HK68	IN	6.3 × 10^5 TCID50	10 d
Milner, 2015	49	Mouse	14–16	M	DIO	HFD	H1N1 influenza A	CA/09	IN	5.8 × 10^5	14 d
	50	Mouse	14–16	M	DIO	HFD	H1N1 influenza A	CA/09	IN	1.3 × 10^3	14 d
	51	Mouse	13–16	M	Gen	LepR^H-/-	H1N1 influenza A	CA/09	IN	5.8 × 10^5	14 d
	52	Mouse	13–16	F	Gen	LepR^H-/-	H1N1 influenza A	CA/09	IN	5.8 × 10^5	14 d

B6-ob/ob: leptin-deficient mice; B6Ay10m and 12m: 10- and 12-week-old agouti peptide positive hyperphagic mice; CPE: lack functional carboxypeptidase enzyme; db/db: leptin receptor-deficient mice; DC: diet composition; DIO: diet-induced obesity; Exp: experiment; F: female; Gen: genetic-induced obesity; GT: genotype; HFD35: 35% of the energy from fat; HFD60: 60% of the energy from fat; HFD: high-fat diet; HFD-P: primed with virus; HFD-UP: unprimed; HFDP: polyunsaturated; HFDS-HP: high protein-to-carbohydrate ratio; HFDS-LP: low protein-to-carbohydrate ratio; HFDS: saturated; HFDw6: omega-6 fatty acid rich; IN: intranasal; IP: intraperitoneal; IT: intubation; IV: intravenous; LepR^H-/-: lack leptin receptor signaling in hypothalamic neurons; M: male; n/a: not applicable; ob/ob: leptin-deficient mice; PO: oral administration; wk: week. Oseltamivir treatment administered to animals.