Publications (31) View all
-
Article: Mechanisms of weight maintenance under high‐ and low‐protein, low‐glycaemic index diets
[show abstract] [hide abstract]
ABSTRACT: Scope: Weight maintenance after intended weight loss is a challenge in an obesogenic environment. In a large multicentre dietary intervention study (DiOGenes), it has recently been demonstrated that a high-protein/low-glycaemic index (HP/LGI) diet was slightly more efficient in maintaining weight loss than low-protein/LGI or high-GI (LP/LGI or HGI) diets. Here, we use a proteomic approach to assess the molecular mechanisms behind this positive effect.Methods and results: A subset of the most successful (weight loser, n=12) and unsuccessful (weight re-gainer, n=12) individuals consuming the LGI diets with either high- or low-protein content (HP or LP/LGI), following an initial calorie deficit run-in weight loss phase, were analyzed at the plasma protein level. Proteomic analysis revealed 18 proteins regulated after 6 months of the dietary weight maintenance phase. Furthermore, 12 proteins were significantly regulated as a function of success rate under an HP diet, arising as candidate biomarkers of mechanisms of successful weight maintenance under an HP/LGI diet. Pregnancy-zone protein (PZP) and protein S (PROS1) were revealed as novel biomarkers of weight maintenance showing opposite effects.Conclusion: Semantic network analysis of the 12 regulated proteins revealed that under an HP/LGI an anti-atherogenic effect and alterations of fat metabolism were associated with the success of maintaining the initial weight loss.Molecular Nutrition & Food Research 09/2011; 55(11):1603 - 1612. · 4.30 Impact Factor -
Article: Six weeks' sebacic acid supplementation improves fasting plasma glucose, HbA1c and glucose tolerance in db/db mice.
[show abstract] [hide abstract]
ABSTRACT: To investigate the impact of chronic ingestion of sebacic acid (SA), a 10-carbon medium-chain dicarboxylic acid, on glycaemic control in a mouse model of type 2 diabetes (T2D). Three groups of 15 db/db mice were fed for 6 weeks either a chow diet (Ctrl) or a chow diet supplemented with 1.5 or 15% (SA(1.5%) and SA(15%) , respectively) energy from SA. Fasting glycaemia was measured once a week and HbA1c before and after supplementation. An oral glucose tolerance test (OGTT) was performed at the end of the supplementation. Gene expression was determined by transcriptomic analysis on the liver of the Ctrl and SA(15%) groups. After 42 days of supplementation, fasting glycaemia and HbA1c were ∼70 and 25% lower in the SA(15%) group compared with the other groups showing a beneficial effect of SA on hyperglycaemia. During OGTT, plasma glucose area under the curve was reduced after SA(15%) compared with the other groups. This effect was associated with a tendency for an improved insulin response. In the liver, Pck1 and FBP mRNA were statistically decreased in the SA(15%) compared with Ctrl suggesting a reduced hepatic glucose output induced by SA. Dietary supplementation of SA largely improves glycaemic control in a mouse model of T2D. This beneficial effect may be due to (i) an improved glucose-induced insulin secretion and (ii) a reduced hepatic glucose output.Diabetes Obesity and Metabolism 12/2010; 12(12):1120-6. · 3.38 Impact Factor -
Article: Transcriptome and translational signaling following endurance exercise in trained skeletal muscle: impact of dietary protein.
[show abstract] [hide abstract]
ABSTRACT: Postexercise protein feeding regulates the skeletal muscle adaptive response to endurance exercise, but the transcriptome guiding these adaptations in well-trained human skeletal muscle is uncharacterized. In a crossover design, eight cyclists ingested beverages containing protein, carbohydrate and fat (PTN: 0.4, 1.2, 0.2 g/kg, respectively) or isocaloric carbohydrate and fat (CON: 1.6, 0.2 g/kg) at 0 and 1 h following 100 min of cycling. Biopsies of the vastus lateralis were collected at 3 and 48 h following to determine the early and late transcriptome and regulatory signaling responses via microarray and immunoblot. The top gene ontology enriched by PTN were: muscle contraction, extracellular matrix--signaling and structure, and nucleoside, nucleotide, and nucleic acid metabolism (3 and 48 h); developmental processes, immunity, and defense (3 h); glycolysis, lipid and fatty acid metabolism (48 h). The transcriptome was also enriched within axonal guidance, actin cytoskeletal, Ca2+, cAMP, MAPK, and PPAR canonical pathways linking protein nutrition to exercise-stimulated signaling regulating extracellular matrix, slow-myofibril, and metabolic gene expression. At 3 h, PTN attenuated AMPKα1Thr172 phosphorylation but increased mTORC1Ser2448, rps6Ser240/244, and 4E-BP1-γ phosphorylation, suggesting increased translation initiation, while at 48 h AMPKα1Thr172 phosphorylation and PPARG and PPARGC1A expression increased, supporting the late metabolic transcriptome, relative to CON. To conclude, protein feeding following endurance exercise affects signaling associated with cell energy status and translation initiation and the transcriptome involved in skeletal muscle development, slow-myofibril remodeling, immunity and defense, and energy metabolism. Further research should determine the time course and posttranscriptional regulation of this transcriptome and the phenotype responding to chronic postexercise protein feeding.Physiological Genomics 07/2011; 43(17):1004-20. · 2.73 Impact Factor -
Article: Influence of gut microbiota on mouse B2 B cell ontogeny and function.
[show abstract] [hide abstract]
ABSTRACT: A complex interplay between the microbiota and the host immune system is evidenced to shape the immune system throughout life, but little is known about the microbial effect on key players of the adaptive immune system, the B2 B cells. In the presented study, we have evaluated the effect of commensal bacteria on B cell ontogeny and function, with the focus on B2 B cells of spleen and Peyer's patches. We have compared germ-free mice to mice that are exposed to a normal complex bacterial community from the day of birth and combined classical immunological assessment with advanced genome-wide expression profiling. Despite a preservation of all B cell subsets and phenotype, our results show that microbiota strongly impact mucosal B cell physiology and lead to higher serum Ig concentrations. We show that this microbial influence comprises downregulation of transcription factors involved in early B cell activation steps and upregulation of genes and proteins involved in later stages of B cell response. In summary, we show an influence of the gut microbiota on function of mucosal B2 B cells, involving mechanisms downstream of B cell activation and proliferation.Molecular Immunology 02/2011; 48(9-10):1091-101. · 2.90 Impact Factor -
Article: Germ-free C57BL/6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolism.
[show abstract] [hide abstract]
ABSTRACT: Recent studies showed that germ-free (GF) mice are resistant to obesity when consuming a high-fat, high-carbohydrate Western diet. However, it remains unclear what mechanisms are involved in the antiobesity phenotype and whether GF mice develop insulin resistance and dyslipidemia with high-fat (HF) feeding. In the present study, we compared the metabolic consequences of HF feeding on GF and conventional (conv) C57BL/6J mice. GF mice consumed fewer calories, excreted more fecal lipids, and weighed significantly less than conv mice. GF/HF animals also showed enhanced insulin sensitivity with improved glucose tolerance, reduced fasting and nonfasting insulinemia, and increased phospho-Akt((Ser-473)) in adipose tissue. In association with enhanced insulin sensitivity, GF/HF mice had reduced plasma TNF-α and total serum amyloid A concentrations. Reduced hypercholesterolemia, a moderate accretion of hepatic cholesterol, and an increase in fecal cholesterol excretion suggest an altered cholesterol metabolism in GF/HF mice. Pronounced nucleus SREBP2 proteins and up-regulation of cholesterol biosynthesis genes indicate that enhanced cholesterol biosynthesis contributed to the cholesterol homeostasis in GF/HF mice. Our results demonstrate that fewer calorie consumption and increased lipid excretion contributed to the obesity-resistant phenotype of GF/HF mice and reveal that insulin sensitivity and cholesterol metabolism are metabolic targets influenced by the gut microbiota.The FASEB Journal 12/2010; 24(12):4948-59. · 5.71 Impact Factor
