PKR is not obligatory for high-fat diet-induced obesity and its associated metabolic and inflammatory complications

Area of Science:

• Biochemistry
• Metabolism
• Immunology

Background:

• Protein kinase R (PKR) has been implicated in mediating adverse effects of high-fat diets (HFD).
• Previous research shows considerable variability in metabolic outcomes following PKR deletion.
• The precise role of PKR in diet-induced metabolic dysfunction remains unclear.

Purpose of the Study:

• To re-evaluate the role of PKR in HFD-induced obesity and metabolic complications in vivo.
• To investigate the putative lipid-sensing role of PKR in vitro.
• To clarify PKR's involvement in inflammation triggered by saturated fatty acids.

Main Methods:

• Utilized PKR knockout (PKR KO) and wild-type (WT) mouse models fed a high-fat diet.
• Assessed obesity, hepatic steatosis, glucose metabolism, and adipose tissue inflammation.
• Examined inflammatory responses in WT and PKR KO macrophages treated with palmitate in vitro.

Main Results:

• PKR deletion did not alter HFD-induced obesity, hepatic steatosis, or glucose metabolism.
• Adipose tissue inflammation was only modestly affected by PKR deletion.
• Palmitate treatment induced similar inflammation levels in WT and PKR KO macrophages, indicating PKR is dispensable for lipid-sensing.

Conclusions:

• PKR does not play a critical role in the development of obesity or associated metabolic complications driven by HFD.
• PKR is not required for macrophages to sense and respond to pro-inflammatory saturated fatty acids.
• These findings challenge the established role of PKR in metabolic disease pathogenesis and lipid-induced inflammation.