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Authors = Peter J. Holst ORCID = 0000-0002-1279-304X

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14 pages, 633 KB  
Article
One Year’s Treatment with the Glucagon-Like Peptide 1 Receptor Agonist Liraglutide Decreases Hepatic Fat Content in Women with Nonalcoholic Fatty Liver Disease and Prior Gestational Diabetes Mellitus in a Randomized, Placebo-Controlled Trial
by Louise Vedtofte, Emilie Bahne, Signe Foghsgaard, Jonatan I. Bagger, Camilla Andreasen, Charlotte Strandberg, Peter M. Gørtz, Jens J. Holst, Henning Grønbæk, Jens A. Svare, Tine D. Clausen, Elisabeth R. Mathiesen, Peter Damm, Lise L. Gluud, Filip K. Knop and Tina Vilsbøll
J. Clin. Med. 2020, 9(10), 3213; https://doi.org/10.3390/jcm9103213 - 6 Oct 2020
Cited by 22 | Viewed by 4934
Abstract
Prior gestational diabetes mellitus (pGDM) is associated with increased risk of nonalcoholic fatty liver disease (NAFLD). Treatment with glucagon-like peptide 1 (GLP-1) receptor agonists has shown beneficial effects in NAFLD patients. We evaluated the effect of the GLP-1 analogue liraglutide on NAFLD features [...] Read more.
Prior gestational diabetes mellitus (pGDM) is associated with increased risk of nonalcoholic fatty liver disease (NAFLD). Treatment with glucagon-like peptide 1 (GLP-1) receptor agonists has shown beneficial effects in NAFLD patients. We evaluated the effect of the GLP-1 analogue liraglutide on NAFLD features in women with pGDM. Eighty-two overweight/obese, nondiabetic women with pGDM were included. We performed abdominal ultrasound, transient elastography with controlled attenuation parameter (CAP), and blood sampling at baseline and after 1 year. Thirty-seven women were randomized to liraglutide (1.8 mg once-daily) and 45 to placebo. Based on the ultrasound scan, 18 women (22%) had ultrasound-verified NAFLD at baseline and of these, 10 (56%) received liraglutide treatment. After 1 year, eight participants no longer had steatosis, four in each treatment group. The number of participants who developed NAFLD was similar in the two treatment groups; five in the liraglutide group and six in the placebo group (p = 0.74). Compared to placebo, liraglutide reduced the CAP-assessed intrahepatic fat content (−28 (−44;−11) vs. 2 (−13;18) dB/m, p < 0.01) and body weight (−4.7 (−6.4;−2.9) vs. −1.4 (−3;0.3) kg, p < 0.01). One-year’s liraglutide treatment had no effect on the presence of ultrasound-diagnosed NAFLD in overweight/obese nondiabetic women with pGDM, but reduced body weight and steatosis assessed by transient elastography with CAP. Full article
(This article belongs to the Special Issue Challenges in Nonalcoholic Steatohepatitis)
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16 pages, 2463 KB  
Article
Effects of a High-Protein/Moderate-Carbohydrate Diet on Appetite, Gut Peptides, and Endocannabinoids—A Preview Study
by Lea Tischmann, Mathijs Drummen, Blandine Gatta-Cherifi, Anne Raben, Mikael Fogelholm, Bolette Hartmann, Jens J. Holst, Isabelle Matias, Daniela Cota, Ronald P. Mensink, Peter J. Joris, Margriet S. Westerterp-Plantenga and Tanja C. Adam
Nutrients 2019, 11(10), 2269; https://doi.org/10.3390/nu11102269 - 21 Sep 2019
Cited by 19 | Viewed by 9650
Abstract
Favorable effects of a high-protein/moderate-carbohydrate (HP/MCHO) diet after weight loss on body weight management have been shown. To extend these findings, associations between perception of hunger and satiety with endocannabinoids, and with glucagon-like peptide-1 (GLP-1) and polypeptide YY (PYY) were assessed. At approximately [...] Read more.
Favorable effects of a high-protein/moderate-carbohydrate (HP/MCHO) diet after weight loss on body weight management have been shown. To extend these findings, associations between perception of hunger and satiety with endocannabinoids, and with glucagon-like peptide-1 (GLP-1) and polypeptide YY (PYY) were assessed. At approximately 34 months after weight loss, 22 female and 16 male participants (mean age 64.5 ± 5.9 years; body mass index (BMI) 28.9 ± 3.9 kg/m2) completed a 48 h respiration chamber study. Participants were fed in energy balance with a HP/MCHO diet with 25%:45%:30% or a moderate-protein/high-carbohydrate (MP/HCHO) diet with 15%:55%:30% of energy from protein:carbohydrate:fat. Endocannabinoids and related compounds, relevant postprandial hormones (GLP-1, PYY), hunger, satiety, and ad libitum food intake were assessed. HP/MCHO versus MP/HCHO reduced hunger perception. The lower decremental area under the curve (dAUC) for hunger in the HP/MCHO diet (−56.6% compared to MP, p < 0.05) was associated with the higher AUC for 2-arachidonoylglycerol (2-AG) concentrations (p < 0.05). Hunger was inversely associated with PYY in the HP/MCHO group (r = −0.7, p < 0.01). Ad libitum food intake, homeostatic model assessment for insulin resistance (HOMA-IR) and incremental AUCs for gut peptides were not different between conditions. HP/MCHO versus MP/HCHO diet-induced reduction in hunger was present after 34 months weight maintenance in the post-obese state. HP/MCHO diet-induced decrease of hunger is suggested to interact with increased 2-AG and PYY concentrations. Full article
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17 pages, 4016 KB  
Review
Virus-Like-Vaccines against HIV
by Anne-Marie C. Andersson, Melanie Schwerdtfeger and Peter J. Holst
Vaccines 2018, 6(1), 10; https://doi.org/10.3390/vaccines6010010 - 11 Feb 2018
Cited by 24 | Viewed by 7636
Abstract
Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus-like-particle (VLP) vaccines have [...] Read more.
Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus-like-particle (VLP) vaccines have emerged as potent inducers of antibody and helper T cell responses, while replication-deficient viral vectors have yielded potent cytotoxic T cell responses. Here, we review the emerging concept of merging these two technologies into virus-like-vaccines (VLVs) for the targeting of HIV. Such vaccines are immunologically perceived as viruses, as they infect cells and produce VLPs in situ, but they only resemble viruses, as the replication defective vectors and VLPs cannot propagate an infection. The inherent safety of such a platform, despite robust particle production, is a distinct advantage over live-attenuated vaccines that must balance safety and immunogenicity. Previous studies have delivered VLVs encoded in modified Vaccinia Ankara vectors and we have developed the concept into a single-reading adenovirus-based technology capable of eliciting robust CD8+ and CD4+ T cells responses and trimer binding antibody responses. Such vaccines offer the potential to display the naturally produced immunogen directly and induce an integrated humoral and cellular immune response. Full article
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12 pages, 1741 KB  
Review
Future Prospects for the Development of Cost-Effective Adenovirus Vaccines
by Cyrielle Fougeroux and Peter J. Holst
Int. J. Mol. Sci. 2017, 18(4), 686; https://doi.org/10.3390/ijms18040686 - 23 Mar 2017
Cited by 43 | Viewed by 7238
Abstract
Vaccination is one of the most efficient tools for disease prevention, and a continuously growing field of research. However, despite progress, we still need more efficient and cost-effective vaccines that would improve access to those in need. In this review, we will describe [...] Read more.
Vaccination is one of the most efficient tools for disease prevention, and a continuously growing field of research. However, despite progress, we still need more efficient and cost-effective vaccines that would improve access to those in need. In this review, we will describe the status of virus-vectored vaccine technology with a focus on adenoviral-based vaccines. Adenovirus (Ad) vaccines have proven to be efficient in military vaccinations against Ad4 and Ad7 and as highly efficient vectored vaccines against rabies. The question of how other adenovirus-based vaccines can become as efficient as the rabies vaccine is the underlying theme in this review. Here, we will first give an overview of the basic properties of vectored vaccines, followed by an introduction to the characteristics of adenoviral vectors and previously tested modifications of the vector backbone and expression cassettes, with a focus on how they can contribute to increased vaccine cost-effectiveness. Finally, we will highlight a few successful examples of research that have attempted to improve the use of adenoviral-based vaccines by improving the transgene immunogenicity. Full article
(This article belongs to the Special Issue Advances in Cheap Vaccines for Public Goods)
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