Perivascular adipose tissue control of insulin-induced vasoreactivity in muscle is impaired in db/db mice
Rick I Meijer1, Wineke Bakker, Caro-Lynn A F Alta
1Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
Abstract:
Microvascular recruitment in muscle is a determinant of insulin sensitivity. Whether perivascular adipose tissue (PVAT) is involved in disturbed insulin-induced vasoreactivity is unknown, as are the underlying mechanisms. This study investigates whether PVAT regulates insulin-induced vasodilation in muscle, the underlying mechanisms, and how obesity disturbs this vasodilation. Insulin-induced vasoreactivity of resistance arteries was studied with PVAT from C57BL/6 or db/db mice. PVAT weight in muscle was higher in db/db mice compared with C57BL/6 mice. PVAT from C57BL/6 mice uncovered insulin-induced vasodilation; this vasodilation was abrogated with PVAT from db/db mice. Blocking adiponectin abolished the vasodilator effect of insulin in the presence of C57BL/6 PVAT, and adiponectin secretion was lower in db/db PVAT. To investigate this interaction further, resistance arteries of AMPKα2(+/+) and AMPKα2(-/-) were studied. In AMPKα2(-/-) resistance arteries, insulin caused vasoconstriction in the presence of PVAT, and AMPKα2(+/+) resistance arteries showed a neutral response. On the other hand, inhibition of the inflammatory kinase Jun NH(2)-terminal kinase (JNK) in db/db PVAT restored insulin-induced vasodilation in an adiponectin-dependent manner. In conclusion, PVAT controls insulin-induced vasoreactivity in the muscle microcirculation through secretion of adiponectin and subsequent AMPKα2 signaling. PVAT from obese mice inhibits insulin-induced vasodilation, which can be restored by inhibition of JNK.
Insights
Perivascular adipose tissue (PVAT) controls muscle insulin sensitivity. In obesity, PVAT impairs insulin-induced vasodilation, but inhibiting JNK can restore this function via adiponectin and AMPK signaling.
Area of Science:
- Physiology
- Metabolic Research
- Vascular Biology
Background:
- Insulin sensitivity is crucial for muscle microvascular function.
- The role of perivascular adipose tissue (PVAT) in insulin-induced vasoreactivity and its disruption in obesity remain unclear.
- Understanding these mechanisms is vital for metabolic health.
Purpose of the Study:
- To investigate if PVAT regulates insulin-induced vasodilation in muscle.
- To elucidate the underlying mechanisms, including the role of adiponectin and AMPK signaling.
- To determine how obesity-associated changes in PVAT affect insulin vasoreactivity.
Main Methods:
- Studied insulin-induced vasoreactivity of resistance arteries with PVAT from lean (C57BL/6) and obese (db/db) mice.
- Investigated the effects of blocking adiponectin and inhibiting Jun NH2-terminal kinase (JNK).
- Utilized AMPKα2(+/+) and AMPKα2(-/-) mouse models to assess signaling pathways.
Main Results:
- PVAT from lean mice facilitated insulin-induced vasodilation, while PVAT from obese mice abrogated it.
- Adiponectin blockade abolished insulin vasodilation in lean PVAT; obese PVAT showed lower adiponectin secretion.
- JNK inhibition in obese PVAT restored insulin vasodilation in an adiponectin-dependent manner, linked to AMPKα2 signaling.
Conclusions:
- PVAT critically controls muscle microcirculation's insulin-induced vasoreactivity.
- Obesity-associated PVAT impairs insulin vasodilation through reduced adiponectin and altered signaling.
- Targeting JNK in PVAT offers a potential therapeutic strategy to restore insulin sensitivity in obesity.
Related Concept Videos
01:24Type II Diabetes II: Pathophysiology
01:26Type I Diabetes II: Pathophysiology