Mildly elevated liver lipid content is characterised by reduced insulin sensitivity

Area of Science:

• Metabolic research
• Endocrinology
• Cardiovascular health

Background:

• A new cut-off of ≤1.85% for normal liver lipid content was recently proposed.
• Individuals with liver lipid between 1.86% and 5.56% showed lower insulin sensitivity compared to those with ≤1.85%.

Purpose of the Study:

• To evaluate tissue-specific insulin sensitivity differences between individuals with low (LL; ≤1.85%) and mildly elevated (MEL; >1.85% and ≤5.56%) liver lipids.

Main Methods:

• Cross-sectional study of 202 White Europeans without diabetes.
• Liver lipids measured by magnetic resonance spectroscopy.
• Endogenous glucose production (EGP) and adipose tissue insulin resistance assessed using hyperinsulinaemic-euglycaemic clamp with PET imaging and fasting free fatty acids, respectively.

Main Results:

• The MEL group exhibited higher EGP during hyperinsulinemia (p=0.041) and increased adipose tissue insulin resistance (p=0.037) compared to the LL group.
• Elevated serum triglycerides and branched-chain amino acids were observed in the MEL group (FDR <0.05).

Conclusions:

• Individuals with MEL have reduced hepatic and adipose tissue insulin sensitivity and adverse metabolic profiles compared to those with LL.
• Findings support a lower upper limit for normal liver lipids in White Europeans.
• Impaired EGP suppression and insulin resistance in lipolysis are early indicators of systemic insulin resistance.