Abstract
The prevalence of metabolic diseases is growing worldwide. Accumulating evidence suggests that solute carrier (SLC) transporters contribute to the etiology of various metabolic diseases. Consistent with metabolic characteristics, the top five organs in which SLC transporters are highly expressed are the kidney, brain, liver, gut, and heart. We aim to understand the molecular mechanisms of important SLC transporter-mediated physiological processes and their potentials as drug targets. SLC transporters serve as ‘metabolic gate’ of cells and mediate the transport of a wide range of essential nutrients and metabolites such as glucose, amino acids, vitamins, neurotransmitters, and inorganic/metal ions. Gene-modified animal models have demonstrated that SLC transporters participate in many important physiological functions including nutrient supply, metabolic transformation, energy homeostasis, tissue development, oxidative stress, host defense, and neurological regulation. Furthermore, the human genomic studies have identified that SLC transporters are susceptible or causative genes in various diseases like cancer, metabolic disease, cardiovascular disease, immunological disorders, and neurological dysfunction. Importantly, a number of SLC transporters have been successfully targeted for drug developments. This review will focus on the current understanding of SLCs in regulating physiology, nutrient sensing and uptake, and risk of diseases.
Highlights
A complex system exists for maintaining human health that consists of dietary components, environmental chemicals, and pharmaceuticals that interact with genes for normal activity
There has been much research that has been performed regarding the various nutrients and metabolites required for health, considerably less focus has been placed on their transport in the body
The transmembrane transport by solute carrier (SLC) could be mainly divided into four modes of transport, including cotransporter, exchanger, facilitated transporter, and orphan transporter (Figure 2)
Summary
Accumulating evidence suggests that solute carrier (SLC) transporters contribute to the etiology of various metabolic diseases. We aim to understand the molecular mechanisms of important SLC transporter-mediated physiological processes and their potentials as drug targets. Gene-modified animal models have demonstrated that SLC transporters participate in many important physiological functions including nutrient supply, metabolic transformation, energy homeostasis, tissue development, oxidative stress, host defense, and neurological regulation. The human genomic studies have identified that SLC transporters are susceptible or causative genes in various diseases like cancer, metabolic disease, cardiovascular disease, immunological disorders, and neurological dysfunction. A number of SLC transporters have been successfully targeted for drug developments. This review will focus on the current understanding of SLCs in regulating physiology, nutrient sensing and uptake, and risk of diseases
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