Liraglutide pharmacotherapy reduces body weight and improves glycaemic control in juvenile obese/hyperglycaemic male and female rats

Abstract

Aims: To examine whether the glucagon-like peptide-1 receptor agonist liraglutide could be used in juvenile male and female rats as an anti-obesity/diabetic pharmaceutical to prevent not only adolescent obesity/hyperglycaemia, but also early-adult onset obesity. Material and Methods: Pregnant dams were fed either standard chow or a high-fat, highsucrose diet (HFSD) from gestational day 2, throughout pregnancy and lactation. Offspring were weaned onto the respective maternal diet. Juveniles received daily subcutaneous injection of liraglutide (50 μg/kg, from postnatal day [PND]30 to PND40 and 200 μg/kg from PND40 to PND60) or vehicle. Food intake, body weight and glycaemic levels were evaluated across the experimental period.Results: Chronic liraglutide administration in juveniles prevented body weight gain in males and retained a normoglycaemic profile in both male and female rats.Conclusion: These preclinical data suggest that maternal and early-life consumption of an HFSD increases caloric intake, body weight gain and hyperglycaemia, a collective set of unwanted metabolic effects that appear to be treatable in juveniles with liraglutide pharmacotherapy intervention. K E Y W O R D Sanimal pharmacology, GLP-1 analogue, liraglutide, neuropharmacology

Early life overnutrition impairs plasticity of non-neuronal brainstem cells and drives obesity in offspring across development in rats

“…To address these two interrelated missing pieces of information, we exposed pregnant dams to HFSD beginning at GD14 to evaluate overnutrition during the last 1/3 timeperiod of gestation and produce a paradigm whereby the dams maintained on HFSD do not gain significantly more weight than those maintained on chow. No difference was detected in the body weight of the dams throughout pregnancy despite greater daily caloric intake, suggesting that dams consuming HFSD might have greater energy expenditure [41][42][43]. The implications of this paradigm point to in utero and early postnatal overnutrition as a driving factor promoting excessive body weight gain, maladaptive alterations in metabolic plasma hormonal levels and the potentially detrimental plasticity changes observed in various DVC glial cells of juvenile male and female rats.…”

Liraglutide suppresses obesity and promotes browning of white fat via miR-27b in vivo and in vitro

“…For example, previous research demonstrated that liraglutide reduced body weight and maintained blood glucose within the normal range in rats. 29 In addition, liraglutide has been shown to decrease serum lipid profiles. 30 This current study showed that liraglutide reduced body weight, blood glucose and TG levels in HF diet-fed rats.…”

A novel strategy for production of liraglutide precursor peptide and development of a new long-acting incretin mimic

“…The Intraperitoneal glucose tolerance tests (IPGTT) was conducted on 6-weeks old BALB/c male mice (weighting 20–27 g) that had fasted for six hours according to the protocol reported previously [ 46 , 47 ]. Briefly, the mice were subjected to 12/12 hours of light/dark cycle and were given free access to standard food and water.…”

“…They were also randomly divided into control and test groups (n = 6), while each group was administered 1.5 mg/g body weight glucose into the intraperitoneal cavity. The treatment group received a single dose injection of the LPP (dissolved in 10 mM Phosphate-Buffered Saline (PBS) at pH 7.4) via intraperitoneal (IP) injection at a concentration of 200 μg/Kg body weight [ 47 , 48 ] and the control group received an equivalent amount of PBS. Before the injection, the glucose concentration in the collected blood samples from the cut tail vein was measured for 30 min.…”

“…Before the injection, the glucose concentration in the collected blood samples from the cut tail vein was measured for 30 min. After injection, the blood glucose was measured for each mice at 0, 10, 20, 30, 40, 50, 60, 90, 120 minutes with a GDH blood glucose meter (TD-4277) [ 47 , 49 ]. The blood-glucose-lowering activity of αB-lir (1.4 mg/Kg body weight) was also tested in mice, using the same procedure with the exception that the protein injection was done 24 hours before the test.…”