Recent research highlights the challenge of defining excess intrahepatic triglyceride (IHTG) levels in nonalcoholic fatty liver disease (NAFLD), emphasizing the need to distinguish between population norms and health-based thresholds. While 5-6% IHTG is often considered the upper limit in healthy cohorts, metabolic abnormalities can emerge at lower levels. A study of 352 adults revealed that adipose tissue insulin resistance (IR) correlates strongly with IHTG, muscle IR peaks at an IHTG of 4.2%, and liver fat’s effect on very-low-density lipoprotein (VLDL) secretion plateaus around 8%. Hepatic insulin sensitivity, however, remains stable across IHTG levels.

These findings position liver fat as a marker of systemic metabolic dysfunction rather than a direct cause. While 4-8% IHTG is a suitable threshold for diagnosing NAFLD, earlier metabolic disruptions suggest the need for refined criteria. The study’s limitations, including its cross-sectional design and lack of racial diversity data, highlight the need for further research. Addressing drivers like adipose tissue inflammation and visceral adiposity is essential for effective treatment, as liver fat serves as a sensitive indicator of broader metabolic dysfunction and systemic health.

Reference: Rotman Y, Neuschwander-Tetri BA. Liver fat accumulation as a barometer of insulin responsiveness again points to adipose tissue as the culprit. Hepatology. 2017 Apr;65(4):1088-1090. doi: 10.1002/hep.29094. Epub 2017 Mar 3. PMID: 28152575; PMCID: PMC5360493.