Transient receptor potential channels and energy homeostasis

Abstract

Transient receptor potential (TRP) channels are members of an ancient class of ion channels that are present in most mammalian tissues. Consistent with their wide tissue distribution, TRPs are capable of influencing diverse physiological processes including adipocyte function, energy intake and energy expenditure. TRPs function as transduction channels downstream of G-protein-coupled receptors (GPCRs) and receptor tyrosine kinases, and some can also be direct sensors of chemical irritants that influence food intake or regulate body temperature and thermogenesis. TRP agonists were shown to reduce body weight and adiposity, suggesting that they might be exploited as therapeutic targets. In this review I discuss the current knowledge of how TRP channels influence energy balance.

Figure 1. Phylogenetic tree showing the human TRP channel superfamily

TRPs are divided in to 6 groups: TRPC (Canonical), TRPV (Vanilloid), TRPM (Melastatin), TRPA (Ankyrin), TRPML (Mucolipin) and TRPP (Polycystin). Functionally, TRPs are non-selective cation channels, mostly present in the plasma membrane, that admit Na⁺ and Ca²⁺ ions into cells. TRPs implicated in energy homeostasis are highlighted in bold.

Figure 2. Temperature-sensitive TRPs trigger thermogenesis

TRPM8 (cold and menthol sensor) and TRPV1 (heat and capsaicin sensor) channels are expressed on sensory afferent nerves that innervate skin and gut mucosa. TRPM8 is a critical detector of environmental cold and triggers reflex sympathetic thermogenesis in brown adipose tissue (BAT). TRPV1 located in the gut monitors core body temperature and triggers both heat loss (sweating) and heat gain (thermogenic) responses. The latter occurs via sympathetic-adrenal stimulation of epinephrine secretion.

Figure 3. Signaling pathways for TRP channels in white and brown adipocytes

In WAT, heteromeric TRPC1/TRPC5 channels function to inhibit adiponectin, a key anti-inflammatory adipokine. Further, TRPV4 channels stimulate pro-inflammatory pathways and inhibit gene programming for oxidative metabolism. In BAT, signaling via TRPM8 channels increases expression of UCP1 and thermogenesis.