Adrenoceptor‐related decrease in serum triglycerides is independent of PPARα activation

Abstract

Adrenoceptor (AR)‐linked pathways belong to the major components of the stress response system and are associated with the pathophysiology of diseases within the spectrum of metabolic syndrome. In this study, the role of adrenoceptor stimulation in serum triglyceride (TG) regulation in mice was investigated. For this purpose, α1‐ARs were activated with phenylephrine (PH) and β1/2‐ARs with isoprenaline (ISOP). Both AR agonists markedly reduced serum TG levels independently of PPARα activation. These drugs also significantly activated the hormone‐sensitive lipase in the white adipose tissue indicating increased mobilization of TGs in this tissue. In addition, PH and ISOP up‐regulated Lpl, Nr4A, Dgat1, Mttp, Aadac and Cd36 genes, critical in TG regulation, whereas the observed decrease in serum TG levels was independent of the hepatic very low‐density lipoprotein (VLDL)‐TG secretion. Interestingly, PH and ISOP also inactivated the hepatic insulin/PI3k/AKT/FoxO1 signaling pathway, holding a critical role in the regulation of genes involved in TG synthesis. Taken together, the findings of the present study indicate that stimulation of α1‐ and β1/2‐ARs markedly reduced serum TG steady‐state levels as a result of alterations in TG synthesis, uptake, transport, hydrolysis, metabolism and clearance, an effect induced by PPARα independent mechanisms.

Daily injection of the β2 adrenergic agonist clenbuterol improved poor muscle growth and body composition in lambs following heat stress-induced intrauterine growth restriction

“…A small number of growth and metabolic outputs that were not influenced by the IUGR condition were responsive to β2 adrenergic stimulation, which was expected. For example, reduced circulating concentrations of glucose and triglycerides were consistent with the known effects of β2 adrenergic agonists (Konstandi et al, 2019;Kalinovich et al, 2020;van Beek et al, 2023). Likewise, the modest increase in circulating Ca 2+ concentrations, greater loin eye area, and reduced backfat thickness were also consistent with outcomes of supplementing β2 agonists as growth promotors in uncompromised animals (Muir, 1988;Bell et al, 1998;Byrem et al, 1998).…”

Role of thermogenic adipose tissue in lipid metabolism and atherosclerotic cardiovascular disease: lessons from studies in mice and humans

“…28 Second, sympathetic stimulation of the liver induces the incorporation of triglycerides into very LDLs (VLDLs) and their release into the circulation, as shown in mice. 29 In humans, this is reflected in an increase in large VLDL particles upon cold exposure. 30 Finally, sympathetic stimulation of BAT promotes lipoprotein lipase (LPL)-mediated uptake of triglyceride-derived FAs from TRLs as demonstrated in mice.…”

Targeting Adrenergic Receptors in Metabolic Therapies for Heart Failure

“…α 1 -AR agonists have also been shown to reduce serum triglycerides [ 290 ]. In a metabolomic analysis, the α 1A -AR selective agonist, A61603, produced a reduction in polyunsaturated fatty acids in the heart [ 291 ]. While there is a report that the α 1B -AR KO mice had impaired glucose homeostasis, insulin resistance and reduced glycogen synthesis [ 292 ], the phenotype only appeared when the mice were fed a high fat diet.…”