TY - JOUR
T1 - Dissociation Between Intrahepatic Triglyceride Content and Insulin Resistance in Familial Hypobetalipoproteinemia
AU - Amaro, Anastassia
AU - Fabbrini, Elisa
AU - Kars, Marleen
AU - Yue, Pin
AU - Schechtman, Kenneth
AU - Schonfeld, Gustav
AU - Klein, Samuel
N1 - Funding Information:
Funding This study was supported by National Institutes of Health grants DK 37948 , DK 56341 (Nutrition and Obesity Research Center), RR024992 (Clinical and Translational Science Award), and RR-00954 (Biomedical Mass Spectrometry Resource).
PY - 2010/7
Y1 - 2010/7
N2 - 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 [μmol · kg fat-free mass-1 · min-1] × 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.
AB - 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 [μmol · kg fat-free mass-1 · min-1] × 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.
KW - Clamp
KW - Insulin sensitivity
KW - Obesity
KW - Steatosis
UR - http://www.scopus.com/inward/record.url?scp=77953893410&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2010.03.039
DO - 10.1053/j.gastro.2010.03.039
M3 - Article
C2 - 20303351
AN - SCOPUS:77953893410
SN - 0016-5085
VL - 139
SP - 149
EP - 153
JO - Gastroenterology
JF - Gastroenterology
IS - 1
ER -