Anti-obesogenic and hypolipidemic effects of a glucagon-like peptide-1 receptor agonist derived from the saliva of the Gila monster

Rafael

Behavioural Pharmacology

et al. 2023

Self Cite

Here, we investigate the effects of obesity induced by monosodium glutamate (MSG) on cognitive impairment and whether this model induces any alteration in the affinity, density, and subtypes of muscarinic acetylcholine receptors (mAChRs) in rat hippocampus. Healthy rats were used as controls, and MSG-obese rats were selected via the Lee index > 0.300. The effects of MSG-induced obesity on hippocampal spatial learning and memory processes were evaluated by using the working memory versions of the Morris’ water maze task and the evaluation of mAChRs by binding assay and their subtypes by immunoprecipitation assays. [3H]Quinuclidinyl benzilate specific binding analysis showed that the equilibrium dissociation constant (KD) did not differ between control and MSG, indicating that affinity is not affected by obesity induced by MSG. The maximum number of binding sites (Bmax) obtained in MSG subjects was lower than that obtained from control rats, indicating a decrease in the expression of total mAChRs. Immunoprecipitation assays reveal a decrease in the expression of M1 subtype of MSG when compared with control rats (M2 to M5 subtypes did not differ between control and MSG). We also observed that MSG promotes a disruption of the spatial working memory which was accompanied by a decrease in the M1 mAChR subtype in rat hippocampus, thus suggesting deleterious long-term effects besides the obesity. In conclusion, these findings provide new insights into how obesity can influence spatial learning and memory that is hippocampal-dependent. The data suggest that the M1 mAChR subtype protein expression is a potential therapeutic target.

Section: Obesity Induced By L-glutamic Acid Monosodium Saltmentioning

confidence: 99%

The M1-muscarinic acetylcholine receptor subtype may play a role in learning and memory performance in the hippocampus of neonatal monosodium glutamate-obese rats

Rafael

Behavioural Pharmacology

et al. 2023

Self Cite

“…Exenatide (synthetic exendin-4 from Gila monster, Heloderma suspectum) is the first glucagon-like-peptide-1 (GLP-1) analogue (Furman, 2012) and has been used as an adjuvant in the treatment of type 2 diabetes mellitus (Nauck et al, 2007;Henry et al, 2014). It presents a combination of actions: stimulation of insulin and suppression of glucagon secretion that result in blood glucose control, and reduction of body weight and cardiovascular risk factors (Eng et al, 1992;Greig et al, 1999;Alves et al, 2017).…”

Section: Approved Drugsmentioning

confidence: 99%

From Animal Poisons and Venoms to Medicines: Achievements, Challenges and Perspectives in Drug Discovery

et al. 2020

“…Animal studies have shown an improvement in blood function, beta cells, and an increase in beta-cell mass after treatment with exenatide [ 93 ]. GLP-1R agonists are promising anti-obesogenic and anti-dyslipidemia drugs in the early stages of obesity, in which the integrity of the nervous system has not been affected [ 94 ]. Currently, exenatide is available commercially under the names Byetta™ and Bydureon™.…”

Section: Nanosystems and Nanocarriersmentioning

confidence: 99%

Nanobiotechnology with Therapeutically Relevant Macromolecules from Animal Venoms: Venoms, Toxins, and Antimicrobial Peptides

et al. 2022

Some diseases of uncontrolled proliferation such as cancer, as well as infectious diseases, are the main cause of death in the world, and their causative agents have rapidly developed resistance to the various existing treatments, making them even more dangerous. Thereby, the discovery of new therapeutic agents is a challenge promoted by the World Health Organization (WHO). Biomacromolecules, isolated or synthesized from a natural template, have therapeutic properties which have not yet been fully studied, and represent an unexplored potential in the search for new drugs. These substances, starting from conglomerates of proteins and other substances such as animal venoms, or from minor substances such as bioactive peptides, help fight diseases or counteract harmful effects. The high effectiveness of these biomacromolecules makes them promising substances for obtaining new drugs; however, their low bioavailability or stability in biological systems is a challenge to be overcome in the coming years with the help of nanotechnology. The objective of this review article is to describe the relationship between the structure and function of biomacromolecules of animal origin that have applications already described using nanotechnology and targeted delivery.