Search Results
You are looking at 1 - 5 of 5 items for
- Author: Jaroslav Kuneš x
- Refine by access: All content x
Search for other papers by Lenka Maletínská in
Google Scholar
PubMed
Search for other papers by Andrea Popelová in
Google Scholar
PubMed
Search for other papers by Blanka Železná in
Google Scholar
PubMed
Institute of Physiology AS CR, Prague, Czech Republic
Search for other papers by Michal Bencze in
Google Scholar
PubMed
Institute of Physiology AS CR, Prague, Czech Republic
Search for other papers by Jaroslav Kuneš in
Google Scholar
PubMed
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder in the elderly population. Numerous epidemiological and experimental studies have demonstrated that patients who suffer from obesity or type 2 diabetes mellitus have a higher risk of cognitive dysfunction and AD. Several recent studies demonstrated that food intake-lowering (anorexigenic) peptides have the potential to improve metabolic disorders and that they may also potentially be useful in the treatment of neurodegenerative diseases. In this review, the neuroprotective effects of anorexigenic peptides of both peripheral and central origins are discussed. Moreover, the role of leptin as a key modulator of energy homeostasis is discussed in relation to its interaction with anorexigenic peptides and their analogs in AD-like pathology. Although there is no perfect experimental model of human AD pathology, animal studies have already proven that anorexigenic peptides exhibit neuroprotective properties. This phenomenon is extremely important for the potential development of new drugs in view of the aging of the human population and of the significantly increasing incidence of AD.
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Search for other papers by Jaroslav Kuneš in
Google Scholar
PubMed
Search for other papers by Veronika Pražienková in
Google Scholar
PubMed
Search for other papers by Andrea Popelová in
Google Scholar
PubMed
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Search for other papers by Barbora Mikulášková in
Google Scholar
PubMed
University of Chemistry and Technology, Prague, Czech Republic
Search for other papers by Jana Zemenová in
Google Scholar
PubMed
Search for other papers by Lenka Maletínská in
Google Scholar
PubMed
Obesity is an escalating epidemic, but an effective noninvasive therapy is still scarce. For obesity treatment, anorexigenic neuropeptides are promising tools, but their delivery from the periphery to the brain is complicated because peptides have a low stability and limited ability to cross the blood–brain barrier. In this review, we summarize results of several studies with our newly designed lipidized analogs of prolactin-releasing peptide (PrRP). PrRP is involved in feeding and energy balance regulation as demonstrated by obesity phenotypes of both PrRP- and PrRP-receptor-knockout mice. Lipidized PrRP analogs showed binding affinity and signaling in PrRP receptor-expressing cells similar to natural PrRP. Moreover, these analogs showed high binding affinity also to anorexigenic neuropeptide FF (NPFF)-2 receptor. Acute peripheral administration of myristoylated and palmitoylated PrRP analogs to mice and rats induced strong and long-lasting anorexigenic effects and neuronal activation in the brain areas involved in food intake regulation. Two-week-long subcutaneous administration of palmitoylated PrRP31 and myristoylated PrRP20 lowered food intake, body weight, improved metabolic parameters and attenuated lipogenesis in mice with diet-induced obesity. A strong anorexigenic, body weight-reducing and glucose tolerance-improving effect of palmitoylated-PrRP31 was shown also in diet-induced obese rats after its repeated 2-week-long peripheral administration. Thus, the strong anorexigenic and body weight-reducing effects of palmitoylated PrRP31 and myristoylated PrRP20 make these analogs attractive candidates for antiobesity treatment. Moreover, PrRP receptor might be a new target for obesity therapy.
Search for other papers by Ivana Vaněčková in
Google Scholar
PubMed
Search for other papers by Lenka Maletínská in
Google Scholar
PubMed
Search for other papers by Michal Behuliak in
Google Scholar
PubMed
Search for other papers by Veronika Nagelová in
Google Scholar
PubMed
Search for other papers by Josef Zicha in
Google Scholar
PubMed
Search for other papers by Jaroslav Kuneš in
Google Scholar
PubMed
Hypertension is one of the major risk factors of cardiovascular diseases, but despite a century of clinical and basic research, the discrete etiology of this disease is still not fully understood. The same is true for obesity, which is recognized as a major global epidemic health problem nowadays. Obesity is associated with an increasing prevalence of the metabolic syndrome, a cluster of risk factors including hypertension, abdominal obesity, dyslipidemia, and hyperglycemia. Epidemiological studies have shown that excess weight gain predicts future development of hypertension, and the relationship between BMI and blood pressure (BP) appears to be almost linear in different populations. There is no doubt that obesity-related hypertension is a multifactorial and polygenic trait, and multiple potential pathogenetic mechanisms probably contribute to the development of higher BP in obese humans. These include hyperinsulinemia, activation of the renin–angiotensin–aldosterone system, sympathetic nervous system stimulation, abnormal levels of certain adipokines such as leptin, or cytokines acting at the vascular endothelial level. Moreover, some genetic and epigenetic mechanisms are also in play. Although the full manifestation of both hypertension and obesity occurs predominantly in adulthood, their roots can be traced back to early ontogeny. The detailed knowledge of alterations occurring in the organism of experimental animals during particular critical periods (developmental windows) could help to solve this phenomenon in humans and might facilitate the age-specific prevention of human obesity-related hypertension. In addition, better understanding of particular pathophysiological mechanisms might be useful in so-called personalized medicine.
Faculty of Chemical Technology, University of Chemistry and Technology Prague, Prague, Czech Republic
Search for other papers by Martina Bugáňová in
Google Scholar
PubMed
Search for other papers by Helena Pelantová in
Google Scholar
PubMed
Search for other papers by Martina Holubová in
Google Scholar
PubMed
Search for other papers by Blanka Šedivá in
Google Scholar
PubMed
Search for other papers by Lenka Maletínská in
Google Scholar
PubMed
Search for other papers by Blanka Železná in
Google Scholar
PubMed
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Search for other papers by Jaroslav Kuneš in
Google Scholar
PubMed
Faculty of Chemical Technology, University of Chemistry and Technology Prague, Prague, Czech Republic
Search for other papers by Petr Kačer in
Google Scholar
PubMed
Search for other papers by Marek Kuzma in
Google Scholar
PubMed
Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
Search for other papers by Martin Haluzík in
Google Scholar
PubMed
Liraglutide is the glucagon-like peptide-1 receptor agonist widely used for the treatment of type 2 diabetes mellitus. Recently, it has been demonstrated to decrease cardiovascular morbidity and mortality in patients with type 2 diabetes and high cardiovascular risk. Although the major modes of liraglutide action are well-known, its detailed action at the metabolic level has not been studied. To this end, we explored the effect of 2-week liraglutide treatment in C57BL/6 male mice with obesity and diabetes induced by 13 weeks of high-fat diet using NMR spectroscopy to capture the changes in urine metabolic profile induced by the therapy. The liraglutide treatment decreased body and fat pads weight along with blood glucose and triglyceride levels. NMR spectroscopy identified 11 metabolites significantly affected by liraglutide treatment as compared to high-fat diet-fed control group. These metabolites included ones involved in nicotinamide adenine dinucleotide metabolism, β-oxidation of fatty acids and microbiome changes. Although majority of the metabolites changed after liraglutide treatment were similar as the ones previously identified after vildagliptin administration in a similar mouse model, the changes in creatinine, taurine and trigonelline were specific for liraglutide administration. The significance of these changes and its possible use in the personalization of antidiabetic therapy in humans requires further research.
Search for other papers by Martina Holubová in
Google Scholar
PubMed
Department of Analytical Chemistry, University of Chemistry and Technology, Prague, Czech Republic
Search for other papers by Jana Zemenová in
Google Scholar
PubMed
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Search for other papers by Barbora Mikulášková in
Google Scholar
PubMed
Search for other papers by Vladimíra Panajotova in
Google Scholar
PubMed
Search for other papers by Jiří Stöhr in
Google Scholar
PubMed
Search for other papers by Martin Haluzík in
Google Scholar
PubMed
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Search for other papers by Jaroslav Kuneš in
Google Scholar
PubMed
Search for other papers by Blanka Železná in
Google Scholar
PubMed
Search for other papers by Lenka Maletínská in
Google Scholar
PubMed
Anorexigenic neuropeptides produced and acting in the brain have the potential to decrease food intake and ameliorate obesity, but are ineffective after peripheral application, owing to a limited ability to cross the blood–brain barrier. We have designed lipidized analogs of prolactin-releasing peptide (PrRP), which is involved in energy balance regulation as demonstrated by obesity phenotypes of both Prrp-knockout and Prrp receptor-knockout mice. The aim of this study was to characterize the subchronic effect of a palmitoylated PrRP analog in two rat models of obesity and diabetes: diet-induced obese Sprague–Dawley rats and leptin receptor-deficient Zucker diabetic (ZDF) rats. In the rats with diet-induced obesity (DIO), a two-week intraperitoneal treatment with palmitoylated PrRP lowered food intake by 24% and body weight by 8%. This treatment also improved glucose tolerance and tended to decrease leptin levels and adipose tissue masses in a dose-dependent manner. In contrast, in ZDF rats, the same treatment with palmitoylated PrRP lowered food intake but did not significantly affect body weight or glucose tolerance, probably in consequence of severe leptin resistance due to a nonfunctional leptin receptor. Our data indicate a good efficacy of lipidized PrRP in DIO rats. Thus, the strong anorexigenic, body weight-reducing, and glucose tolerance-improving effects make palmitoylated PrRP an attractive candidate for anti-obesity treatment.
