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Gastroenterology. 2010 Jul;139(1):149-53. doi: 10.1053/j.gastro.2010.03.039. Epub 2010 Mar 18.

Dissociation between intrahepatic triglyceride content and insulin resistance in familial hypobetalipoproteinemia.

Author information

1
Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA.

Abstract

BACKGROUND & AIMS:

Hepatic steatosis is associated with insulin resistance, but it is not clear whether increased intrahepatic triglyceride (IHTG) content causes the resistance or is a marker. Subjects with familial hypobetalipoproteinemia (FHBL) have high levels of IHTG because of a genetic defect in hepatic export of triglycerides, and provide a unique cohort to study the relationship between steatosis and insulin sensitivity.

METHODS:

One group of lean subjects with normal IHTG content (2.2% +/- 0.6% of liver volume) (n = 6), and 3 groups of overweight and obese subjects matched for body mass index, were studied: (1) normal IHTG content (3.3% +/- 0.5%; n = 6), (2) high IHTG content (21.4% +/- 2.6%) due to nonalcoholic fatty liver disease (NAFLD; n = 6), and (3) high IHTG content (18.1% +/- 2.2%) due to FHBL (n = 3). A hyperinsulinemic-euglycemic clamp procedure, in conjunction with glucose tracer infusion, was used to determine multiorgan insulin sensitivity.

RESULTS:

Hepatic insulin sensitivity (reciprocal of glucose rate of appearance [micromol x kg fat-free mass(-1) x min(-1)] x insulin [mU/L]) was greatest in the Lean group (2.0 +/- 0.4); it was the same among subjects with FHBL (0.8 +/- 0.1) and the group with normal IHTG content, matched for body mass index (0.7 +/- 0.1), but greater than the NAFLD group (0.3 +/- 0.1) (P < .01). Muscle insulin sensitivity (percent increase in glucose uptake during insulin infusion) was greatest in the Lean group (576% +/- 70%). Muscle insulin sensitivity was similar in subjects with FHBL and those with normal IHTG (319% +/- 77%, 326% +/- 27%, respectively), but greater than the NAFLD group (145% +/- 18%) (P < .01).

CONCLUSIONS:

Steatosis is dissociated from insulin resistance in FHBL, which suggests that increased IHTG content is a marker, not a cause, of metabolic dysfunction.

PMID:
20303351
PMCID:
PMC2902714
DOI:
10.1053/j.gastro.2010.03.039
[Indexed for MEDLINE]
Free PMC Article

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