Liraglutide treatment counteracts alterations in adipose tissue metabolism induced by orchiectomy in rats.

The reduction in androgens serum concentration is a physiological condition that accompanies age advancement but can also occur because of prostate cancer and gender affirming treatment or pathological conditions such as functional hypogonadism. However, androgen deficiency is related to a higher risk of developing metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). Considering that glucagon-like peptide 1 (GLP1) analogs are increasingly used in the treatment of T2DM, we investigated if liraglutide could also attenuate the metabolic changes caused by orchiectomy in rats. Wistar rats were orchiectomized (ORC), and subdivided in four groups: sham saline, sham liraglutide, ORC saline, and ORC liraglutide. After sixty days, metabolic parameters were evaluated in blood, muscle, liver, brown (BAT) and white adipose tissue (WAT) visceral depots. Glucose utilization, oxidation, and conversion to lipids by de novo lipogenesis, and basal and adrenaline-stimulated lipolysis were evaluated in BAT and WAT depots. Orchiectomy increased triglyceridemia, BAT and rtWAT weight, and lipolysis and reduced glucose utilization. Liraglutide treatment reversed these effects. These results indicate that liraglutide improves triglyceridemia and glucose metabolism in WAT depots, which suggests that it may be a promising therapeutic strategy to handle disruptions in energy metabolism caused by androgen deficiency.

Model JFA ，Lima MV ，Ohlweiler R ，Sarapio E ，Vogt ÉL ，Rocha DS ，de Souza SK ，Vinagre AS ... -  《-》

Liraglutide improves lipid and carbohydrate metabolism of ovariectomized rats.

Considering that post-menopausal women and ovariectomized rodents develop obesity associated with increased visceral fat, this study was developed to investigate if liraglutide, a glucagon-like peptide 1 (GLP1) analogue, could improve the metabolism of estrogen (E2) deficient females. Wistar rats were ovariectomized (OVX), and subdivided in four groups: sham saline, sham liraglutide, OVX saline, and OVX liraglutide. After sixty days, metabolic parameters of blood, heart, liver, brown (BAT) and white adipose tissue (WAT) visceral depots, and, heart oxidative homeostasis, were evaluated. Castration increased the animals' body weight, the relative weight of the WAT depots, hepatic triglycerides and cardiac glycogen content. Liraglutide treatment reversed these effects, decreased WAT depots weight and increased glucose oxidation and lipogenesis in BAT and WAT. In addition, liraglutide enhanced adrenalin (A) lipolytic effect. These results indicate that liraglutide may be a promising treatment to restore lipid homeostasis and prevent weight gain associated with E2 deficiency.

Model JFA ，Lima MV ，Ohlweiler R ，Lopes Vogt É ，Rocha DS ，Souza SK ，Türck P ，Araújo ASDR ，Vinagre AS ... -  《-》

The key role of a glucagon-like peptide-1 receptor agonist in body fat redistribution.

Zhao L ，Zhu C ，Lu M ，Chen C ，Nie X ，Abudukerimu B ，Zhang K ，Ning Z ，Chen Y ，Cheng J ，Xia F ，Wang N ，Jensen MD ，Lu Y ... -  《-》

Cooperative role of the glucagon-like peptide-1 receptor and β3-adrenergic-mediated signalling on fat mass reduction through the downregulation of PKA/AKT/AMPK signalling in the adipose tissue and muscle of rats.

To explore the cooperation of GLP-1 receptor and β3-adrenergic receptor (β3-AR)-mediated signalling in the control of fat mass/feeding behaviour by studying the effects of a combined therapy composed of the GLP-1R agonist liraglutide and the β3-AR agonist CL316243. The study included the analysis of key mechanisms regulating lipid/cholesterol metabolism, and thermogenesis in brown (BAT) and epididymal white (eWAT) adipose tissues, abdominal muscle and liver of male rats. CL316243 (1 mg kg-1 ) and liraglutide (100 μg kg-1 ) co-administration over 6 days potentiated an overall negative energy balance (reduction in food intake, body weight gain, fat/non-fat mass ratio, liver fat content, and circulating levels of non-essential fatty acids, triglycerides, very low-density lipoprotein-cholesterol and leptin). These effects were accompanied by increased plasma levels of insulin and IL6. We also observed increased gene expression of uncoupling proteins regulating thermogenesis in BAT/eWAT (Ucp1) and muscle (Ucp2/3). Expression of transcription factor and enzymes involved either in de novo lipogenesis (Chrebp, Acaca, Fasn, Scd1, Insig1, Srebp1) or in fatty acid β-oxidation (Cpt1b) was enhanced in eWAT and/or muscle but decreased in BAT. Pparα and Pparγ, essentials in lipid flux/storage, were decreased in BAT/eWAT but increased in the muscle and liver. Cholesterol synthesis regulators (Insig2, Srebp2, Hmgcr) were particularly over-expressed in muscle. These GLP-1R/β3-AR-induced metabolic effects were associated with the downregulation of cAMP-dependent signalling pathways (PKA/AKT/AMPK). Combined activation of GLP-1 and β3-ARs potentiate changes in peripheral pathways regulating lipid/cholesterol metabolism in a tissue-specific manner that favours a switch in energy availability/expenditure and may be useful for obesity treatment.

Decara J ，Rivera P ，Arrabal S ，Vargas A ，Serrano A ，Pavón FJ ，Dieguez C ，Nogueiras R ，Rodríguez de Fonseca F ，Suárez J ... -  《-》

Ovariectomy-Induced Hepatic Lipid and Cytochrome P450 Dysmetabolism Precedes Serum Dyslipidemia.

Malinská H ，Hüttl M ，Miklánková D ，Trnovská J ，Zapletalová I ，Poruba M ，Marková I ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》