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Abstract 637: Exercise-stimulated Resolvin Biosynthesis In Adipose Tissue Is Prevented By High Fat Diet-induced Adrenergic Insufficiency
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Diet-induced adipose tissue (AT) inflammation is associated with obesity and the development of systemic insulin resistance. Our lab has shown that specialized proresolving mediators (SPMs), which are induced by exercise (Exe), restore insulin sensitivity and promote resolution of adipose tissue resolution. In this study, we sought to determine if exercise-enhanced production of SPMs extends to adipose tissue and has dietary dependence. Compared with sedentary controls (Sed), mice exposed to 4 wk of Exe display elevated AT expression of SPM biosynthetic enzyme
Alox15
(Sed 1.12±0.18 vs. Exe 1.68±0.13 relative expression,
n
=5-7), SPM levels (Sed vs. Exe; RvD1 156.7±12.02 vs. 223.0±24.71; 17
R
-RvD1 354.0±35.86 vs. 534.4±98.92; RvD4 31.31±6.93 vs. 123.1±30.69; and 17
R
-RvD3 2.92±1.08 vs. 8.20±1.70 pg/g,
n
=5-7), and proresolving M2 macrophages (F4/80
+
CD301
+
; Sed 17.5±3.2 vs. Exe 40.9±4.5 %F4/80
+
,
n
=4-6). These changes were dependent upon diet as 6-weeks of high fat diet (60% kcal from fat; HFD) feeding abrogated the proresolving effect of exercise when compared with low fat diet fed (10% kcal from fat; LFD) controls—despite performing the same amount of exercise. Interestingly, exercise-induced epinephrine (Epi) production (LFD Sed 147.2±24.4 vs Exe 312.5±60.9 ng/mL) was inhibited by HFD (Sed 121.1±22.7 vs. Exe 140.0±16.8 ng/mL). HFD feeding resulted in diminished expression of the Epi biosynthetic enzyme phenylethanolamine N-methyltransferase (PNMT) in adrenal glands (protein expression: LFD 1.0±0.25 vs. HFD 0.36±0.15,
n
=4). Moreover, Sed HFD fed animals treated with Epi (0.1 mg/kg i.p. daily) for 1 wk display increased abundance of proresolving adipose tissue macrophages (F4/80
+
CD301
+
; Sed 17.8±0.6 vs. Exe 25.2±3.1 %F4/80
+
,
n
=6-7). These results suggest that the resolution promoting effect of exercise in adipose tissue is controlled by high fat diet consumption and adrenergic stimulation.
Ovid Technologies (Wolters Kluwer Health)
Title: Abstract 637: Exercise-stimulated Resolvin Biosynthesis In Adipose Tissue Is Prevented By High Fat Diet-induced Adrenergic Insufficiency
Description:
Diet-induced adipose tissue (AT) inflammation is associated with obesity and the development of systemic insulin resistance.
Our lab has shown that specialized proresolving mediators (SPMs), which are induced by exercise (Exe), restore insulin sensitivity and promote resolution of adipose tissue resolution.
In this study, we sought to determine if exercise-enhanced production of SPMs extends to adipose tissue and has dietary dependence.
Compared with sedentary controls (Sed), mice exposed to 4 wk of Exe display elevated AT expression of SPM biosynthetic enzyme
Alox15
(Sed 1.
12±0.
18 vs.
Exe 1.
68±0.
13 relative expression,
n
=5-7), SPM levels (Sed vs.
Exe; RvD1 156.
7±12.
02 vs.
223.
0±24.
71; 17
R
-RvD1 354.
0±35.
86 vs.
534.
4±98.
92; RvD4 31.
31±6.
93 vs.
123.
1±30.
69; and 17
R
-RvD3 2.
92±1.
08 vs.
8.
20±1.
70 pg/g,
n
=5-7), and proresolving M2 macrophages (F4/80
+
CD301
+
; Sed 17.
5±3.
2 vs.
Exe 40.
9±4.
5 %F4/80
+
,
n
=4-6).
These changes were dependent upon diet as 6-weeks of high fat diet (60% kcal from fat; HFD) feeding abrogated the proresolving effect of exercise when compared with low fat diet fed (10% kcal from fat; LFD) controls—despite performing the same amount of exercise.
Interestingly, exercise-induced epinephrine (Epi) production (LFD Sed 147.
2±24.
4 vs Exe 312.
5±60.
9 ng/mL) was inhibited by HFD (Sed 121.
1±22.
7 vs.
Exe 140.
0±16.
8 ng/mL).
HFD feeding resulted in diminished expression of the Epi biosynthetic enzyme phenylethanolamine N-methyltransferase (PNMT) in adrenal glands (protein expression: LFD 1.
0±0.
25 vs.
HFD 0.
36±0.
15,
n
=4).
Moreover, Sed HFD fed animals treated with Epi (0.
1 mg/kg i.
p.
daily) for 1 wk display increased abundance of proresolving adipose tissue macrophages (F4/80
+
CD301
+
; Sed 17.
8±0.
6 vs.
Exe 25.
2±3.
1 %F4/80
+
,
n
=6-7).
These results suggest that the resolution promoting effect of exercise in adipose tissue is controlled by high fat diet consumption and adrenergic stimulation.
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