Hepatic Diacylglycerol-Associated Protein Kinase Cε Translocation Links Hepatic Steatosis to Hepatic Insulin Resistance in Humans.
Level 4 - case-series / case-control
Cross-sectional observational human study with subgroup tissue biopsy analysis
PubMed 28591572 · doi:10.1016/j.celrep.2017.05.035
What was done
Researchers evaluated the relationship between liver fat and tissue-specific insulin sensitivity in 133 obese individuals. To investigate the molecular mechanisms linking steatosis to insulin resistance, they performed detailed lipidomic and molecular analyses on liver biopsy samples from a subset of 29 participants, measuring cytosolic diacylglycerols, ceramides, and protein kinase C epsilon (PKCε) translocation to the plasma membrane.
What was found
Hepatic steatosis was broadly associated with insulin resistance in liver, adipose tissue, and peripheral tissues, but intrahepatic triglyceride levels alone were neither strictly sufficient nor essential for hepatic insulin resistance. In the biopsy subset (n=29), subjects with hepatic insulin resistance showed increased hepatic cytosolic diacylglycerol content and elevated PKCε translocation to the plasma membrane, whereas hepatic ceramide content was not increased. The abstract reports directional associations without providing exact numerical concentrations, ratios, or p-values.
Why it matters
This study provides translational human evidence distinguishing benign triglyceride storage from lipotoxic signaling, identifying hepatic cytosolic diacylglycerols and subsequent PKCε activation—rather than total steatosis or ceramides—as key drivers of liver insulin resistance in non-alcoholic fatty liver disease.
Limits
The study is cross-sectional and observational, preventing definitive causal conclusions. Molecular and biopsy assessments were performed in a small subset (n=29) of the original cohort, and the study population was restricted entirely to obese individuals.
Cited by
- contradicts Insulin resistance is caused by a receptor shutdown driven by excessive insulin stimulation from high carbohydrate intake or frequent eating.