Olivier Aprikian

Rosemary (Rosmarinus officinalis L.) leaf extract limits weight gain and liver steatosis in mice fed a high-fat diet.

The objective of this study was to investigate the effects of rosemary (Rosmarinus officinalis L.) leaf extract (RE) on the prevention of weight gain and associated metabolic disorders in mice fed a high-fat diet. For this purpose, RE was administered for 50 days at 20 or 200 mg/kg body weight (BW) to mice fed a high-fat diet. Body weight was monitored during the study and body composition was measured before and at the end of the intervention. Glucose tolerance, assessed by an intraperitoneal glucose tolerance test (IPGTT), and hepatic and faecal lipid contents were determined at the end of the study. Treatment with 200 mg/kg BW of RE induced a significant reduction of weight and fat mass gain (-64% and -57%, respectively) associated with an increase of faecal lipid excretion. This effect appears to be related to the inhibition of pancreatic lipase activity induced by RE, as demonstrated IN VITRO. While glucose tolerance and fasting glycaemia were not affected by RE treatment, hepatic triglyceride levels were decreased by 39% in RE-treated mice. Administration of the lower dose of RE (20 mg/kg BW) was ineffective on all the parameters measured. In conclusion, our results demonstrate that consumption of 200 mg/kg BW of RE can limit weight gain induced by a high-fat diet and protect against obesity-related liver steatosis.

Adipose tissue plasticity during catch-up fat driven by thrifty metabolism: Relevance for muscle-adipose glucose redistribution during catch-up growth

OBJECTIVE Catch-up growth, a risk factor for later type 2 diabetes, is characterized by hyperinsulinemia, accelerated body-fat recovery (catch-up fat), and enhanced glucose utilization in adipose tissue. Our objective was to characterize the determinants of enhanced glucose utilization in adipose tissue during catch-up fat. RESEARCH DESIGN AND METHODS White adipose tissue morphometry, lipogenic capacity, fatty acid composition, insulin signaling, in vivo glucose homeostasis, and insulinemic response to glucose were assessed in a rat model of semistarvation-refeeding. This model is characterized by glucose redistribution from skeletal muscle to adipose tissue during catch-up fat that results solely from suppressed thermogenesis (i.e., without hyperphagia). RESULTS Adipose tissue recovery during the dynamic phase of catch-up fat is accompanied by increased adipocyte number with smaller diameter, increased expression of genes for adipogenesis and de novo lipogenesis, increased fatty acid synthase activity, increased proportion of saturated fatty acids in triglyceride (storage) fraction but not in phospholipid (membrane) fraction, and no impairment in insulin signaling. Furthermore, it is shown that hyperinsulinemia and enhanced adipose tissue de novo lipogenesis occur concomitantly and are very early events in catch-up fat. CONCLUSIONS These findings suggest that increased adipose tissue insulin stimulation and consequential increase in intracellular glucose flux play an important role in initiating catch-up fat. Once activated, the machinery for lipogenesis and adipogenesis contribute to sustain an increased insulin-stimulated glucose flux toward fat storage. Such adipose tissue plasticity could play an active role in the thrifty metabolism that underlies glucose redistribution from skeletal muscle to adipose tissue.

Comparison of two models of intrauterine growth restriction for early catch-up growth and later development of glucose intolerance and obesity in rats.

Two models of intrauterine growth restriction, maternal food restriction (FR), and dexamethasone (DEX) exposure were compared for early postnatal catch-up growth and later development of glucose intolerance and obesity in Sprague-Dawley rats. Mated dams were randomly divided into three groups at 10 days gestational age. Group FR was food restricted (50% of nongestating rats) during the last 11 days of gestation; Group DEX received DEX injections during the last week of gestation, and Group CON, the control group, had no intervention. Birth weight, catch-up growth, body weight, and food intake were measured in male offspring for 22 wk. Body composition, blood glucose, and plasma insulin in response to a glucose load were assessed at 8, 16, and 22 wk. Pups from both FR and DEX dams had similarly lower birth weights than CON (22% and 25%, P < 0.0001), but catch-up growth, which occurred during the suckling period, was much more rapid in FR than DEX offspring (6 vs. 25 days, 95% CI). Postweaning, there were no significant differences between groups in food intake, body weight, body fat, and plasma insulin, but baseline plasma glucose at 22 wk and 2-h glucose area-under-the-curve at 8 and 22 wk were greater only in FR vs. CON offspring (P < 0.05), thereby contrasting with the lack of significant differences between DEX and CON. These results suggest that prenatal food restriction is a more sensitive model than DEX exposure for studies aimed at investigating the link between low birth weight, early postnatal catch-up growth, and later development of glucose intolerance.

Interleukin-18 protein level is upregulated in adipose tissue of obese mice.

In this study, we investigated the regulation of Interleukin‐18 (IL‐18) and caspase‐1 mRNA and protein levels in adipose and liver tissue of obese (ob/ob) mice compared with ob/+ mice. In ob/ob mice, which have a twofold higher IL‐18 plasma level as compared with lean mice, IL‐18 mRNA expression was significantly reduced by 1.6‐fold in adipose tissue, whereas protein level was enhanced fourfold as compared with ob/+ mice. However, caspase‐1 mRNA expression and activity were significantly enhanced in adipose tissue of ob/ob mice. Conversely, both IL‐18 mRNA and protein levels were slightly enhanced, but caspase‐1 activity was reduced in liver of ob/ob mice as compared with lean mice. In conclusion, we show that adipose and hepatic IL‐18 protein expressions are increased in obese mice. However, in contrast to liver, the adipose IL‐18 protein level appears to be upregulated through a post‐transcriptional mechanism probably involving caspase‐1.

A low α-linolenic intake during early life increases adiposity in the adult guinea pig

BackgroundThe composition of dietary fatty acids (FA) during early life may impact adult adipose tissue (AT) development. We investigated the effects of α-linolenic acid (ALA) intake during the suckling/weaning period on AT development and metabolic markers in the guinea pig (GP).MethodsNewborn GP were fed a 27%-fat diet (w/w %) with high (10%-ALA group), moderate (2.4%-ALA group) or low (0.8%-ALA group) ALA content (w/w % as total FA) until they were 21 days old (d21). Then all animals were switched to a 15%-fat diet containing 2% ALA (as total FA) until 136 days of age (d136).ResultsALA and docosapentaenoic acid measured in plasma triglycerides (TG) at d21 decreased with decreasing ALA intake. Total body fat mass was not different between groups at d21. Adipose tissue TG synthesis rates and proliferation rate of total adipose cells, as assessed by 2H2O labelling, were unchanged between groups at d21, while hepatic de novo lipogenesis was significantly 2-fold increased in the 0.8%-ALA group. In older GP, the 0.8%-ALA group showed a significant 15-%-increased total fat mass (d79 and d107, p < 0.01) and epididymal AT weight (d136) and tended to show higher insulinemia compared to the 10%-ALA group. In addition, proliferation rate of cells in the subcutaneous AT was higher in the 0.8%-ALA (15.2 ± 1.3% new cells/5d) than in the 10%-ALA group (8.6 ± 1.7% new cells/5d, p = 0.021) at d136. AT eicosanoid profiles were not associated with the increase of AT cell proliferation.ConclusionA low ALA intake during early postnatal life promotes an increased adiposity in the adult GP.

The guinea pig as a model for metabolic programming of adiposity

BACKGROUND The human infant accumulates body fat during intrauterine life. The guinea pig shares this characteristic and is born with similar adiposity; thus, it may be a relevant model to study obesity programming. OBJECTIVE The objective of this study was to evaluate guinea pig adipose tissue (AT) development and the effect of a maternal high-fat diet on the offsprings body composition. DESIGN In experiment 1, adipogenesis dynamics were evaluated at 3, 10, 21, and 136 d in epididymal and retroperitoneal AT with the use of (2)H(2)O labeling. In experiment 2, dams received a control or high-fat diet from mating to 21 d after delivery. The offspring received a high-fat diet from 22 to 105 d; adiposity was measured at 2, 21, 54, and 97 d. RESULTS The fractional proliferation rate (FPR) of cells in epididymal AT was 25.2% of cells synthesized in 5 d at 3 d of age and decreased over time (P < 0.001). Age had no effect on retroperitoneal FPR (P = 0.179). In both depots, the fractional synthesis rate (FSR) of palmitate decreased extensively from day 3 to day 10, increasing by day 21 and declining by day 136 (P < 0.001). The FSR of triglycerides decreased with age (P < 0.001). A maternal high-fat diet increased the offsprings adiposity at 2 d and 21 d (P < 0.05) but had no effect on body composition later in life. CONCLUSIONS Adipogenesis in the guinea pig is very active during early life and was altered by a maternal high-fat diet; thus, it is an adequate model for intrauterine fat deposition. However, there were no effects of maternal diet later in life.