Title:Glucocorticoid Excess Induces Accumulation of Cardiac Glycogen and Triglyceride: Suggested Role for AMPK
Volume: 19
Issue: 27
Author(s): Prasanth Puthanveetil and Brian Rodrigues
Affiliation:
Keywords:
Glucocorticoids, Heart, AMPK, Metabolism, Cardiac Dysfunction.
Abstract: Glucocorticoids include steroid hormones released from the adrenal cortex or synthetic analogues developed for various inflammatory
and immune disorders. GCs are known to play an important role in maintaining the body’s metabolic balance, but their irregular
activity has been associated with complications like Cushing’s syndrome, insulin resistance, and heart disease. Conventional GC
action is through their nuclear receptor activation, but specific and non-specific membrane bound receptor mediated non-genomic actions
have also been reported. GCs increase AMPK phosphorylation at Thr172, in addition to augmenting AMPK protein and gene expressions.
AMPK is insulin mimetic in many of its actions like glucose uptake and inhibition of lipolysis, and these properties of AMPK are
made used in conditions like insulin resistance and diabetes. Nevertheless, if AMPK is activated by GC in the absence of diabetes or decreased
insulin signaling, accumulation of substrates in the form of glycogen and triglycerides could precipitate cardiac abnormalities.
Glycogen storage can lead to many disorders like hypertrophy, conduction system disease and Wolff Parkinson White syndrome. TG accumulation
is associated with generation of free radicals, ceramide formation, mitochondrial dysfunction and cardiac cell death. In this
review, we outline the cardiometabolic changes associated with GC, especially related to augmentation in AMPK, and link these changes
to cardiac dysfunction.
