Aquaglyceroporins and
caveolins are submicroscopic
integral membrane proteins that are particularly abundant in many mammalian cells.
Aquaglyceroporins (AQP3, AQP7, AQP9 and AQP10) encompass a subfamily of
aquaporins that allow the movement of water, but also of small solutes, such as
glycerol, across cell membranes.
Glycerol constitutes an important metabolite as a substrate for de novo synthesis of
triacylglycerols and
glucose as well as an energy substrate to produce
ATP via the mitochondrial oxidative phosphorylation. In this sense, the control of
glycerol influx/efflux in metabolic organs by
aquaglyceroporins plays a crucial role with the dysregulation of these
glycerol channels being associated with
metabolic diseases, such as
obesity,
insulin resistance,
non-alcoholic fatty liver disease and
cardiac hypertrophy. On the other hand, caveolae have emerged as relevant plasma membrane sensors implicated in a wide range of cellular functions, including endocytosis, apoptosis,
cholesterol homeostasis, proliferation and signal transduction. Caveolae-coating
proteins, namely
caveolins and cavins, can act as scaffolding
proteins within caveolae by concentrating signaling molecules involved in
free fatty acid and
cholesterol uptake, proliferation,
insulin signaling or vasorelaxation, among others. The importance of caveolae in whole-body homeostasis is highlighted by the link between homozygous mutations in genes encoding
caveolins and cavins with
metabolic diseases, such as
lipodystrophy,
dyslipidemia,
muscular dystrophy and
insulin resistance in rodents and humans. The present review focuses on the role of
aquaglyceroporins and
caveolins on
lipid and
glucose metabolism, insulin secretion and signaling, energy production and cardiovascular homeostasis, outlining their potential relevance in the development and treatment of
metabolic diseases.