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. 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

Anastassia Amaro  1 , Elisa Fabbrini, Marleen Kars, Pin Yue, Kenneth Schechtman, Gustav Schonfeld, Samuel Klein
Affiliations

Dissociation between intrahepatic triglyceride content and insulin resistance in familial hypobetalipoproteinemia

Anastassia Amaro et al. Gastroenterology. 2010 Jul.

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.

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Figures

Figure 1
Figure 1
Hepatic insulin sensitivity calculated as the product of glucose Ra in plasma during the basal stage of the clamp procedure (top panel), muscle insulin sensitivity assessed as the relative increase in glucose rate of disappearance (Rd) during insulin infusion (bottom panel) in subjects with familial hypobetalipoproteinemia (FHBL), normal intrahepatic triglyceride (IHTG) content and nonalcoholic fatty liver disease (NAFLD) and Lean controls (Lean). Values are means±SEM. *P<.01.
See this image and copyright information in PMC

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