Galectin-1 in Obesity and Type 2 Diabetes

Emanuel Fryk, Vagner R R Silva, Per-Anders Jansson, Emanuel Fryk, Vagner R R Silva, Per-Anders Jansson

Abstract

Galectin-1 is a carbohydrate-binding protein expressed in many tissues. In recent years, increasing evidence has emerged for the role of galectin-1 in obesity, insulin resistance and type 2 diabetes. Galectin-1 has been highly conserved through evolution and is involved in key cellular functions such as tissue maturation and homeostasis. It has been shown that galectin-1 increases in obesity, both in the circulation and in the adipose tissue of human and animal models. Several proteomic studies have independently identified an increased galectin-1 expression in the adipose tissue in obesity and in insulin resistance. Large population-based cohorts have demonstrated associations for circulating galectin-1 and markers of insulin resistance and incident type 2 diabetes. Furthermore, galectin-1 is associated with key metabolic pathways including glucose and lipid metabolism, as well as insulin signalling and inflammation. Intervention studies in animal models alter animal weight and metabolic profile. Several studies have also linked galectin-1 to the progression of complications in diabetes, including kidney disease and retinopathy. Here, we review the current knowledge on the clinical potential of galectin-1 in obesity and type 2 diabetes.

Keywords: galectin-1; insulin resistance; obesity; type 2 diabetes.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Galectin-1 in obesity and insulin resistance. (A) Circulating galectin-1 levels are elevated in human obesity (~25% higher in obese vs. lean [64]) and in HFD-fed mice (~50% higher in HFD vs. chow [22]). (B) Circulating galectin-1 is positively associated with serum insulin levels in humans and modulated insulin secretion in mice [64,80]. Further, galectin-1 inversely associates with plasma glucose [64], but galectin-1 reduced glucose uptake in human adipose cells in vitro [15]. Insulin and glucose confer direct stimulatory effects on galectin-1 secretion to cell media from several cell types [71,77,80,94,95,96]. Galectin-1 is positively associated with circulating levels of IL-6, TNF-α and CRP [47,64]. Likewise, triggers of inflammatory pathways up-regulate galectin-1 in several immune cells [97].
Figure 2
Figure 2
Galectin-1 effects in different organs (arrow up or down) reported in pre-clinical studies (animal models and human cells), which should be confirmed in human tissues and clinical studies. Galectin-1 has been shown to improve tissue recovery after a cerebral stroke [101,102]. Galectin-1 also increases neovascularization and unwanted vascular proliferation in diabetic retinopathy [42,103,104]. In the pancreas, galectin-1 has been shown to stimulate insulin secretion in female mice, and circulating galectin-1 is also positively associated with serum insulin in studies in humans [47,64,80]. Studies have linked galectin-1 to adipogenesis, and it has been proposed that galectin-1 could directly affect pparg expression [23,72]. Galectin-1 has also been shown to reduce thermogenesis in mice [23,82]. In the liver, inhibition of galectin-1 results in increased fibrosis and increased severity of hepatitis [105], and galectin-1 reduces inflammation in the heart after ischaemia [106,107]. Galectin-1 also appears to facilitate skeletal muscle regeneration in muscle degenerative conditions, as well as in muscle damage [108]. In the kidney, results have been conflicting, as a Mendelian randomization study in humans and an intervention study in mice have demonstrated kidney protective effects of galectin-1 [43,47]. Conversely, circulating galectin-1 has been associated with a lower kidney function in cross-sectional and longitudinal studies [47,48], and in vitro studies have demonstrated contradicting associations with different fibrotic markers [95,96,109].

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Source: PubMed

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