Distinct Time Course of the Decrease in Hepatic AMP-Activated Protein Kinase and Akt Phosphorylation in Mice Fed a...

Area of Science:

• Metabolism
• Endocrinology
• Molecular Biology

Background:

• Insulin resistance is linked to impaired insulin-Akt signaling pathway.
• The precise timing of AMPK and Akt dephosphorylation during high-fat diet (HFD)-induced obesity and insulin resistance is debated.
• Reversibility of these pathway impairments upon switching from HFD to standard diet (SD) is not well understood.

Purpose of the Study:

• To investigate the time course of AMPK and Akt phosphorylation changes in the liver during HFD-induced obesity and insulin resistance.
• To determine if these impairments are reversible after transitioning from HFD to SD.
• To elucidate the early molecular events in HFD-induced metabolic dysfunction.

Main Methods:

• Male ddY mice were fed either a standard diet (SD) or a high-fat diet (HFD) for durations ranging from 3 to 28 days.
• A separate group was fed HFD for 14 days, followed by SD for 14 days.
• Liver tissue was analyzed for AMPK and Akt expression and phosphorylation levels using immunoblotting.

Main Results:

• HFD feeding for as early as 3 days led to weight gain, hepatic lipid accumulation, and significantly decreased AMPK phosphorylation compared to SD.
• After 14 days on HFD, systemic insulin resistance developed, accompanied by significantly decreased Akt phosphorylation.
• Switching from HFD to SD for 3 days reversed the impairments in AMPK and Akt phosphorylation and ameliorated systemic insulin resistance.

Conclusions:

• AMPK phosphorylation is an early indicator that decreases rapidly upon HFD consumption.
• Akt signaling impairment and insulin resistance manifest later but are reversible with dietary changes.
• Prompt lifestyle modifications are crucial for preventing or mitigating diabetes risk associated with HFD-induced metabolic changes.