Galectin-12: A protein associated with lipid droplets that regulates lipid metabolism and energy balance - PubMed (original) (raw)

Galectin-12: A protein associated with lipid droplets that regulates lipid metabolism and energy balance

Ri-Yao Yang et al. Adipocyte. 2012.

Abstract

Galectin-12, a member of the galectin family of animal lectins, is preferentially expressed in adipocytes. We recently reported that this galectin is localized on lipid droplets, specialized organelles for fat storage. Galectin-12 regulates lipid degradation (lipolysis) by modulating lipolytic protein kinase A (PKA) signaling. Mice deficient in galectin-12 exhibit enhanced adipocyte lipolysis, increased mitochondria respiration, reduced adiposity and ameliorated insulin resistance associated with weight gain. The results suggest that galectin-12 may be a useful target for treatment of obesity-related metabolic conditions, such as insulin resistance, metabolic syndrome, and type 2 diabetes. Most previously described galectins largely reside in the cytosol, although they can also be induced to become associated with membrane-containing structures. Along with an in-depth characterization of galectin-12, this mini-review comments on this first report of a galectin normally localized specifically in an organelle that performs an important intracellular function. Further studies will help shed light on how this protein regulates cellular homeostasis, especially energy homeostasis, and provide additional insight into the intracellular functions of galectins.

Keywords: adipocyte; adipose tissue; galectin; galectin-12; insulin sensitivity; lipid metabolism; lipolysis.

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Figures

Figure 1.

Figure 1.

Galectin structure and function. (A) Galectin subtypes and structural features. Prototypical galectins are composed of a single galectin CRD. The chimeric type of galectin, galectin-3, consists of a N-terminal non-lectin domain in addition to a C-terminal galectin CRD. Tandem repeat type of galectins contains 2 CRDs in tandem connected by a linker sequence. (B) Galectins are synthesized in the cytosol but can also be secreted through poorly-defined mechanisms. Functioning from both outside and inside of the cell, galectins are involved in diverse cellular processes including vesicle trafficking of glycoproteins, chemotaxis, proliferation, pre-RNA splicing, and apoptosis. Extracellular galectins are likely to function by binding to cell surface glycans, while intracellular effectors that mediate galectin function are largely unknown.

Figure 2.

Figure 2.

Role of galectin-12 in the regulation of lipolysis in adipocytes by protein kinase A (PKA) signaling. (A) Lipolysis in a wildtype (Lgals12+/+) adipocyte. PKA is activated by cyclic AMP (cAMP) to set off a signaling cascade that results in the sequential hydrolysis of triglyceride (TG) in the lipid droplet (yellow ball) to free fatty acids (FFAs) and glycerol. In this cell, the lipid droplet protein galectin-12 limits cAMP levels to downregulate PKA activation, most likely by acting on specific phosphodiesterases that degrade cAMP. (B) Ablation of galectin-12 in adipocytes results in elevated concentrations of cAMP, enhanced lipolytic PKA signaling, and therefore augmentation of lipolysis.

References

    1. Havel PJ. Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes. 2004;53(Suppl 1):S143–51. doi: 10.2337/diabetes.53.2007.S143. -DOI -PubMed
    1. Yang RY, Yu L, Graham JL, Hsu DK, Lloyd KC, Havel PJ, et al. Ablation of a galectin preferentially expressed in adipocytes increases lipolysis, reduces adiposity, and improves insulin sensitivity in mice. Proc Natl Acad Sci U S A. 2011;108:18696–701. doi: 10.1073/pnas.1109065108. -DOI -PMC -PubMed
    1. Yang RY, Rabinovich GA, Liu FT. Galectins: structure, function and therapeutic potential. Expert Rev Mol Med. 2008;10:e17. doi: 10.1017/S1462399408000719. -DOI -PubMed
    1. Liu FT, Patterson RJ, Wang JL. Intracellular functions of galectins. Biochim Biophys Acta. 2002;1572:263–73. doi: 10.1016/S0304-4165(02)00313-6. -DOI -PubMed
    1. Liu FT, Rabinovich GA. Galectins as modulators of tumour progression. Nat Rev Cancer. 2005;5:29–41. doi: 10.1038/nrc1527. -DOI -PubMed

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