Metabolic responses of light and taste receptors – unexpected actions of GPCRs in adipocytes

Abstract

The G-protein-coupled receptor (GPCR) superfamily includes sensory receptors that can detect and respond to taste and light. Recent investigations have identified key metabolic roles for such receptors in tissues considered ‘non-sensory’ such as adipose tissue. The major functions of white and brown adipose tissues include energy storage/release and thermogenesis, respectively. These processes are tightly controlled by GPCR pathways that serve to maintain energy homeostasis. Opsins 3 and 4 are GPCRs activated by blue light and in adipocytes control lipolysis as well as affect brown adipocyte activity. Furthermore, Opsin 3 signals to regulate the conversion of white to thermogenic beige/BRITE (Brown-in-white) adipocytes. Taste receptors that respond to fatty acids, sweet and bitter are expressed in adipocytes as well as in taste buds. Ffar2 and the long chain fatty acid receptor GPR120 are highly expressed in white adipocytes and the human tongue. In adipose tissue Ffar2 mediates the metabolic effects of butyrate and propionate produced by the gut microbiome. GPR120 is highly expressed in brown adipose tissue and regulates fatty acid oxidation and mitochondrial function. The type I taste receptor Tas1r3 senses sweet and umami, is expressed in adipocytes and on obesogenic diets Tas1r3 global gene knockout protects from metabolic dysfunction. Type II taste receptors that sense bitter are expressed by adipocytes and bitter agonists have been found to modulate adipocyte differentiation and lipid storage levels. This review explores recent unexpected findings of light and taste receptors in adipocytes and examines effects of their signaling in the control of adipose tissue biology.

G Protein-Coupled Receptors and the Rise of Type 2 Diabetes in Children

“…Animal models demonstrated that a high-fat diet down-modulates OPN3 in white adipocytes, and the latter protects from diet-induced obesity and insulin resistance. Exposing brown adipose tissue to led light leads to an increase in glucose uptake and glucose-dependent mitochondrial respiration in the wild type, whilst cells knocked out for OPN3 did not show any consequence after exposure [ 46 ]. Modern sleep rhythms and over- or under- exposure to blue light are likely to alter opsin stimulation and in turn to contribute to the insurgency of type 2 diabetes.…”

Identification of G Protein-Coupled Receptors (GPCRs) Associated with Lambda-Cyhalothrin Detoxification in Cydia pomonella

“…G protein-coupled receptors (GPCRs), which are known as the most diverse superfamily of membrane receptors, are composed of N-terminal and C-terminal regions alongside a highly conserved seven-transmembrane (7TM) core backbone . Functioning as the primary signaling receptors, GPCRs play critical regulatory functions across a range of physiological processes, including cellular metabolism, hormone secretion, behavioral and emotional regulation, and the immune system. − By manipulating the regulatory actions of GPCRs, it is possible to modulate the normal receptor function, ultimately resulting in the death or decreased reproductive capacity of pests, thereby reducing their populations . It was widely believed that olfactory receptors (ORs) in C. pomonella were G protein-coupled receptors capable of binding to a diverse array of odor molecules, thereby influencing the olfactory perception.…”

Light Sensing beyond Vision: Focusing on a Possible Role for the FICZ/AhR Complex in Skin Optotransduction

“…Although OPN3 is highly expressed in different brain areas, its precise function in these regions remains unidentified, aside from modulating the Acoustic Startle Reflex (ASR), which is an involuntary, rapid contraction of skeletal muscle in response to a sudden, intense auditory stimulus [29]. Notably, in adipocytes, OPN3 has been linked to the conversion of white adipose tissue to thermogenic brown adipose tissue [30], suggesting a thermosensitive nature for OPN3. This could explain its presence in body areas not typically exposed to light rays, such as adipose tissue and even the heart, as described in an interesting article by Prof. de Lauro Castrucci's group [7].…”