Adiponectin treatment attenuates inflammatory response during early sepsis in obese mice

Figures & data

Table 1 Weight in grams and mean arterial blood pressure (MAP) in different groups

	Body weight (g) Mean ± SEM		MAP (mmHg) Mean ± SEM
	CTRL	DIO	CTRL	DIO
Sham	26.75±0.36	36.83±1.07†	61±2.24	65±4.46
Sepsis	26.6±0.3	36.12±0.4†	53.8±1.3*	46.8±1.2*†
Sepsis + adiponectin	27.5±0.2	38.7±2.7†	64.2±4.6#	60.7±0.5#

Notes: Body weight of CTRl and DIO sham, sepsis, and sepsis + adiponectin groups shows no significant differences from each other within the groups, and body weights of DIO mice were significantly higher than their CTRl counterparts. The MAPs in sepsis groups were significantly lower than their respective sham counterparts. The MAPs in sepsis + adiponectin groups were significantly higher compared to sepsis alone in both CTRl and DIO mice. Finally, MAP in DIO-sepsis groups was significantly lower compared to CTRl-sepsis groups.

* P<0.05 vs respective sham;

# P<0.05 vs respective sepsis;

† P<0.05 vs respective CTRl.

Abbreviations: DIO, diet-induced obesity; CTRl, control; SEM, standard error of the mean.

Figure 1 adiponectin decreased leukocyte adhesion in cerebral microcirculation in CTRl and DIO mice with sepsis.

Notes: sepsis-induced leukocyte adhesion in the cerebral microcirculation was significantly increased in DIO and CTRl mice compared to respective sham control. Moreover, the leukocyte adhesion in DIO-sepsis mice was significantly increased compared to the CTRl-sepsis mice. In both the CTRl and DIO mice, the leukocyte adhesion in adiponectin-treated mice was significantly decreased compared to their respective sepsis alone counterparts. leukocyte adhesion in sepsis + adiponectin groups from CTRl vs DIO was not significantly different from one another. *P<0.05 vs respective sham; ^#P<0.05 vs cTRl sepsis; ^† P<0.05 vs respective sepsis.

Abbreviations: CTRl, control diet; DIO, diet-induced obesity.

Figure 2 adiponectin decreased platelet adhesion in cerebral microcirculation in CTRl and DIO mice with sepsis.

Notes: sepsis-induced platelet adhesion in the cerebral microcirculation followed a similar pattern as in the leukocyte adhesion. There was a significant increase in platelet adhesion in both the DIO and CTRl mice compared to the respective sham control. Moreover, the platelet adhesion was significantly increased in DIO-sepsis mice compared to the CTRl-sepsis mice. In both the CTRl and DIO mice, the platelet adhesion in adiponectin-treated mice was significantly decreased compared to their respective sepsis alone counterparts. Platelet adhesion in the sepsis + adiponectin groups from CTRl vs DIO was not significantly different from one another. *P<0.05 vs respective sham; ^#P<0.05 vs CTRl sepsis; ^†P<0.05 vs respective sepsis.

Abbreviations: CTRl, control diet; DIO, diet-induced obesity.

Figure 3 Adiponectin treatment attenuates inflammatory response in fatty acid-fed macrophages.

Notes: We demonstrate that in BMDM cells, FFA treatment significantly increased the TNF-α mRNA expression in response to LPS stimulation. Moreover, we also show that adiponectin treatment attenuated TNF-α mRNA expression in response to LPS stimulation in both the BSA control and FFA-fed macrophages. *P<0.05 vs respective BSA control; ^†P<0.05 vs respective LPS-stimulated group; ^#P<0.05 vs BSA + LPS; ^‡P<0.05 vs BSA + ADN group.

Abbreviations: BSA, bovine serum albumin; FFA, free fatty acid; LPS, lipopolysaccharide; TNF-α, tumor necrosis factor-alpha; ADN, adiponectin.

Figure 4 adiponectin treatment and SIRT1 mRNA expression.

Notes: There was a significant increase in the expression of SIRT1 mRNA in FFA-fed macrophages vs BSA-fed macrophages. Moreover, adiponectin treatment showed decreased SIRT1 mRNA expression in BSA-fed macrophages compared to FFA-fed macrophages; there was a significant increase in SIRT1 mRNA expression with adiponectin treatment. *P<0.05 vs BSA + LPS; ^†P<0.05 vs BSA + LPS + ADN; ^#P<0.05 vs FFA + LPS.

Abbreviations: BSA, bovine serum albumin; FFA, free fatty acid; LPS, lipopolysaccharide; SIRT1, sirtuin-1; ADN, adiponectin.

Figure 5 Bone marrow-derived macrophages with FFA and BSA feeding with and without adiponectin treatment.

Notes: BMDM isolated from WT and SIRT1KO mice showed increased TNF-α mRNA expression in response to LPS after BSA as well as FFA-feeding. adiponectin treatment decreased TNF-α mRNA expression in SIRT1KO mice only in BSA-fed macrophage and not in FFA-fed macrophages. FFA feeding of BMDM showed that there was a significant increase in TNF-α mRNA in both WT and SIRT1KO groups vs respective WT groups. There was a significant increase in TNF-α mRNA in FFA-fed SIRT1KO BMDM vs FFA-fed WT BMDM. adiponectin treatment significantly decreased TNF-α mRNA expression in both WT and SIRT1KO mice with FFA feeding, although the TNF-α mRNA expression in ADN-treated SIRT1KO BMDM remained significantly higher vs WT BMDM. *P<0.05; ****P<0.0001.

Abbreviations: BSA, bovine serum albumin; BMDM, bone marrow-derived macrophages; FFA, free fatty acid; LPS, lipopolysaccharide; TNF-α, tumor necrosis factor-alpha; SIRT1KO, SIRT1 knockout; WT, wild type; SIRT1, sirtuin-1.