Hepatic steatosis does not cause insulin resistance in people with familial hypobetalipoproteinaemia

Item does not contain fulltextAIMS/HYPOTHESIS: Hepatic steatosis is strongly associated with hepatic and whole-body insulin resistance. It has proved difficult to determine whether hepatic steatosis itself is a direct cause of insulin resistance. In patients with familial hypobetalipoproteinaemia (FHBL), hepatic steatosis is a direct consequence of impaired hepatic VLDL excretion, independently of metabolic derangements. Thus, patients with FHBL provide a unique opportunity to investigate the relation between increased liver fat and insulin sensitivity. METHODS: We included seven male participants with FHBL and seven healthy matched controls. Intrahepatic triacylglycerol content and intramyocellular lipid content were measured using localised proton magnetic resonance spectroscopy ((1)H-MRS). A two-step hyperinsulinaemic-euglycaemic clamp, using stable isotopes, was assessed to determine hepatic and peripheral insulin sensitivity. RESULTS: (1)H-MRS showed moderate to severe hepatic steatosis in patients with FHBL. Basal endogenous glucose production (EGP) and glucose levels did not differ between the two groups, whereas insulin levels tended to be higher in patients compared with controls. Insulin-mediated suppression of EGP during lower dose insulin infusion and insulin-mediated peripheral glucose uptake during higher dose insulin infusion were comparable between FHBL participants and controls. Baseline fatty acids and lipolysis (glycerol turnover) at baseline and during the clamp did not differ between groups. CONCLUSIONS/INTERPRETATION: In spite of moderate to severe hepatic steatosis, people with FHBL do not display a reduction in hepatic or peripheral insulin sensitivity compared with healthy matched controls. These results indicate that hepatic steatosis per se is not a causal factor leading to insulin resistance. TRIAL REGISTRATION: ISRCTN35161775

1H-MRS of hepatic fat using short TR at 3T: SNR optimization and fast T2 relaxometry.

Item does not contain fulltextOBJECT: To increase the signal-to-noise ratio (SNR) efficiency of hepatic fat signals in proton magnetic resonance spectroscopy (1H MRS) at 3 T, in order to improve the quantitation of hepatic fat and allow fast, single breath-hold T2 relaxometry of hepatic water and fat. MATERIALS AND METHODS: Since the T1 of lipid protons is relatively short, we hypothesized that it could be possible to increase the lipid SNR efficiency by choosing a TR shorter than that typically employed (>/=1.5 s). The lipid SNR per unit-time was calculated using published values of lipid (CH2)n protons' T1 at 3 T. 1H MRS PRESS spectra were acquired from VOIs located in the right lobe of the liver in 28 healthy volunteers. At the short TR of 0.6 s, fast T2 relaxometry with the acquisition of 16 echo times (30, 40, ..., 180 ms), was performed in a single breath-hold measurement using a modified PRESS sequence. RESULTS: Good agreement was observed between simulated and experimental data, with the shortening of TR to 0.6 s yielding an ~50% SNR improvement of hepatic lipid (CH2)n resonances, compared to the SNR at TR=2 s. The T2 relaxation time of water and lipid (CH2)n protons at 3 T was 25.8+/-1.1 ms and 55.4+/-3.9 ms, respectively, across five healthy volunteers. CONCLUSION: The short-TR approach allows for an improved SNR efficiency of lipids and for fast T2 relaxometry of hepatic water and fat, with a detailed coverage of the T2 relaxation decay curve, within a single breath-hold experiment.1 december 201