Michèle Chabert

Postprandial metabolic and hormonal responses of obese dyslipidemic subjects with metabolic syndrome to test meals, rich in carbohydrate, fat or protein

BACKGROUND The metabolic syndrome (MS) is a cluster of heterogeneous abnormalities conferring increased risk of cardiovascular diseases. Few postprandial studies have been conducted in MS individuals. OBJECTIVES We aimed to study MS subjects with the same abnormalities: abdominal obesity, hypertriglyceridemia and low plasma HDL. We assessed postprandial variations of metabolic parameters related to obesity, dyslipidemia and glucose homeostasis. METHODS In this randomized, double-blind, cross-over study, male MS and control subjects consumed, at separate occasions, a high carbohydrate (HC), high fat (HF) or high protein (HP) breakfast meal providing 30% of each subjects resting energy expenditure. RESULTS Appetite hormones peptide YY and ghrelin did not differ between-subject groups. Interleukin-6 was two-fold higher in MS compared with control subjects, consistently with an inflammatory state. Hypertriglyceridemia of MS subjects was aggravated postprandially with the HF and HP meals and was lowest after the HC meal, arguing against increased hepatic VLDL production. HDL-cholesterol of MS subjects remained low postprandially, whereas apolipoprotein (apo) A-II was higher than in control subjects. Unexpectedly, postprandial insulin and glucose responses were higher in MS compared with control subjects, with the HP meal inducing the greater effects. CONCLUSIONS The sustained postprandial hypertriglyceridemia of MS subjects after all meals suggests defective catabolism of triglyceride-rich lipoproteins. The greater postprandial increases in plasma insulin and glucose in MS relatively to control subjects indicate decreased insulin sensitivity, not revealed in the fasted state.

D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile

Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients.

Transient micro-elastography: A novel non-invasive approach to measure liver stiffness in mice

AIM To develop and validate a transient micro-elastography device to measure liver stiffness (LS) in mice. METHODS A novel transient micro-elastography (TME) device, dedicated to LS measurements in mice with a range of measurement from 1-170 kPa, was developed using an optimized vibration frequency of 300 Hz and a 2 mm piston. The novel probe was validated in a classical fibrosis model (CCl(4)) and in a transgenic murine model of systemic amyloidosis. RESULTS TME could be successfully performed in control mice below the xiphoid cartilage, with a mean LS of 4.4 ± 1.3 kPa, a mean success rate of 88%, and an excellent intra-observer agreement (0.98). Treatment with CCl(4) over seven weeks drastically increased LS as compared to controls (18.2 ± 3.7 kPa vs 3.6 ± 1.2 kPa). Moreover, fibrosis stage was highly correlated with LS (Spearman coefficient = 0.88, P < 0.01). In the amyloidosis model, much higher LS values were obtained, reaching maximum values of > 150 kPa. LS significantly correlated with the amyloidosis index (0.93, P < 0.0001) and the plasma concentration of mutant hapoA-II (0.62, P < 0.005). CONCLUSION Here, we have established the first non-invasive approach to measure LS in mice, and have successfully validated it in two murine models of high LS.

A method for long-term and accurate measurement and recording of the blood glucose level in man

We describe a technique of continuous and long-term withdrawal of venous blood which permits a continuous measurement and recording of the blood glucose level. The preparation and setting up of a special double lumen catheter are detailed. This technique provides very accurate blood glucose time course determination and requires the withdrawal of small amounts of blood.