Publications (29) View all
-
Article: Apolipoprotein A5 deficiency aggravates high-fat diet-induced obesity due to impaired central regulation of food intake.
[show abstract] [hide abstract]
ABSTRACT: Mutations in apolipoprotein A5 (APOA5) have been associated with hypertriglyceridemia in humans and mice. This has been attributed to a stimulating role for APOA5 in lipoprotein lipase-mediated triglyceride hydrolysis and hepatic clearance of lipoprotein remnant particles. However, because of the low APOA5 plasma abundance, we investigated an additional signaling role for APOA5 in high-fat diet (HFD)-induced obesity. Wild-type (WT) and Apoa5(-/-) mice fed a chow diet showed no difference in body weight or 24-h food intake (Apoa5(-/-), 4.5±0.6 g; WT, 4.2±0.5 g), while Apoa5(-/-) mice fed an HFD ate more in 24 h (Apoa5(-/-), 2.8±0.4 g; WT, 2.5±0.3 g, P<0.05) and became more obese than WT mice. Also, intravenous injection of APOA5-loaded VLDL-like particles lowered food intake (VLDL control, 0.26±0.04 g; VLDL+APOA5, 0.11±0.07 g, P<0.01). In addition, the HFD-induced hyperphagia of Apoa5(-/-) mice was prevented by adenovirus-mediated hepatic overexpression of APOA5. Finally, intracerebroventricular injection of APOA5 reduced food intake compared to injection of the same mouse with artificial cerebral spinal fluid (0.40±0.11 g; APOA5, 0.23±0.08 g, P<0.01). These data indicate that the increased HFD-induced obesity of Apoa5(-/-) mice as compared to WT mice is at least partly explained by hyperphagia and that APOA5 plays a role in the central regulation of food intake.-Van den Berg, S. A. A., Heemskerk, M. M., Geerling, J. J., van Klinken, J.-B., Schaap, F. G., Bijland, S., Berbée, J. F. P., van Harmelen, V. J. A., Pronk, A. C. M., Schreurs, M., Havekes, L. M., Rensen, P. C. N., van Dijk, K. W. Apolipoprotein A5 deficiency aggravates high-fat diet-induced obesity due to impaired central regulation of food intake.The FASEB Journal 05/2013; · 5.71 Impact Factor -
Article: Cd36 is important for adipocyte recruitment and affects lipolysis.
[show abstract] [hide abstract]
ABSTRACT: OBJECTIVE: The scavenger receptor CD36 facilitates the cellular uptake of long chain fatty acids. Since CD36-deficiency attenuates the development of high fat diet (HFD)-induced obesity, we set out to characterize the role of CD36-deficiency in preadipocyte recruitment and adipocyte function. DESIGN AND METHODS: Fat cell size and number were determined in gonadal, visceral and subcutaneous adipose tissue of CD36(-/-) and WT mice after six weeks on HFD. Basal lipolysis and insulin-inhibited lipolysis were investigated in gonadal adipose tissue. RESULTS: CD36(-/-) mice showed a reduction in adipocyte size in all fat pads. Gonadal adipose tissue also showed a lower total number of adipocytes due to a lower number of very small adipocytes (diameter <50 µm). This was accompanied by an increased pool of preadipocytes which suggests that CD36-deficiency reduces the capacity of preadipocytes to become adipocytes. Regarding lipolysis, in adipose tissue from CD36(-/-) mice cAMP levels were increased and both basal and 8-bromo-cAMP stimulated lipolysis were higher. However, insulin-mediated inhibition of lipolysis was more potent in CD36(-/-) mice. CONCLUSIONS: These results indicate that during fat depot expansion, CD36-deficiency negatively affects preadipocyte recruitment and that in mature adipocytes, CD36-deficiency is associated with increased basal lipolysis and insulin responsiveness.Obesity 03/2013; · 4.28 Impact Factor -
Article: Practical aspects of estimating energy components in rodents.
[show abstract] [hide abstract]
ABSTRACT: Recently there has been an increasing interest in exploiting computational and statistical techniques for the purpose of component analysis of indirect calorimetry data. Using these methods it becomes possible to dissect daily energy expenditure into its components and to assess the dynamic response of the resting metabolic rate (RMR) to nutritional and pharmacological manipulations. To perform robust component analysis, however, is not straightforward and typically requires the tuning of parameters and the preprocessing of data. Moreover the degree of accuracy that can be attained by these methods depends on the configuration of the system, which must be properly taken into account when setting up experimental studies. Here, we review the methods of Kalman filtering, linear, and penalized spline regression, and minimal energy expenditure estimation in the context of component analysis and discuss their results on high resolution datasets from mice and rats. In addition, we investigate the effect of the sample time, the accuracy of the activity sensor, and the washout time of the chamber on the estimation accuracy. We found that on the high resolution data there was a strong correlation between the results of Kalman filtering and penalized spline (P-spline) regression, except for the activity respiratory quotient (RQ). For low resolution data the basal metabolic rate (BMR) and resting RQ could still be estimated accurately with P-spline regression, having a strong correlation with the high resolution estimate (R (2) > 0.997; sample time of 9 min). In contrast, the thermic effect of food (TEF) and activity related energy expenditure (AEE) were more sensitive to a reduction in the sample rate (R (2) > 0.97). In conclusion, for component analysis on data generated by single channel systems with continuous data acquisition both Kalman filtering and P-spline regression can be used, while for low resolution data from multichannel systems P-spline regression gives more robust results.Frontiers in physiology. 01/2013; 4:94. -
Article: Caspase-1 deficiency in mice reduces triglyceride absorption and hepatic triglyceride secretion.
[show abstract] [hide abstract]
ABSTRACT: Caspase-1 is known to activate the pro-inflammatory cytokines IL-1β and IL-18. Additionally, it can cleave other substrates including proteins involved in metabolism. Recently, we showed that caspase-1-deficiency in mice strongly reduces HFD-induced weight gain, at least partly caused by an increased energy production. Increased feces secretion by caspase-1-deficient mice suggests that lipid malabsorption possibly further reduces adipose tissue mass. In this study we therefore investigated whether caspase-1 plays a role in triglyceride-(TG)-rich-lipoprotein metabolism using caspase-1-deficient and wild-type mice. Caspase-1-deficiency reduced the postprandial TG-response to an oral lipid load, while TG-derived fatty acid (FA) uptake by peripheral tissues was not affected, demonstrated by unaltered kinetics of [3H]TG-labeled VLDL-like-emulsion-particles. An oral gavage of [3H]TG-containing olive oil revealed that caspase-1-deficiency reduced TG absorption and subsequent uptake of TG-derived FA in liver, muscle, and adipose tissue. Similarly, despite an elevated hepatic TG content, caspase-1-deficiency reduced hepatic VLDL-TG production. Intestinal and hepatic gene expression analysis revealed that caspase-1-deficiency did not affect FA oxidation or FA uptake, but rather reduced intracellular FA transport, thereby limiting lipid availability for the assembly and secretion of TG-rich lipoproteins. The current study reveals a novel function for caspase-1, or caspase-1-cleaved substrates, in controlling intestinal TG absorption and hepatic TG secretion.The Journal of Lipid Research 11/2012; · 5.56 Impact Factor -
Article: META060 protects against diet-induced obesity and insulin resistance in a high-fat-diet fed mouse.
[show abstract] [hide abstract]
ABSTRACT: OBJECTIVE: We investigated whether a reduced iso-α acid derived from an extract of Humulus lupulus L., META060, had an effect on weight gain, body composition, and metabolism in a high-fat-diet (HFD) fed mouse model. METHODS: Weight gain was monitored for up to 20 wk in mice receiving a low-fat diet, an HFD, or an HFD supplemented with META060 or rosiglitazone. Body composition was determined using dual-energy x-ray absorptiometric analysis. Indirect calorimetric measurements were performed to investigate the energy balance in the mice, and oral glucose tolerance tests were administered to examine the effect of META060 on the glycemic response. RESULTS: The HFD-fed mice administered META060 for 14 wk had a significantly lower mean weight than HFD-fed mice (30.58 ± 0.5 versus 37.88 ± 0.7 g, P < 0.05). Indirect calorimetric measurements showed an increased metabolic flexibility in mice supplemented with META060. In addition, glucose tolerance was improved, comparable to the effects of rosiglitazone treatment. CONCLUSIONS: META060 has potential therapeutic value for managing obesity and insulin resistance, and further research into the mechanism of action is warranted.Nutrition 09/2012; · 3.03 Impact Factor
