Galectin-12 Is Required for Adipogenic Signaling and Adipocyte Differentiation

Yang, Ri Yao; Hsu, Daniel K.; Yu, Liang; Chen, Huan Yuan; Liu, Fu Tong

doi:10.1074/jbc.m401303200

Cited by 69 publications

(82 citation statements)

References 70 publications

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“…1C) in adipose tissue. This finding suggests that adipogenesis is largely normal in Lgals12 −/− mice, despite previous observations that galectin-12 expression was required for the adipocyte differentiation of 3T3-L1 cells in vitro (15). The absence of an overt adipo- genic phenotype in vivo may be explained by genetic robustness against null mutations in the germ line (33).…”

Section: Discussioncontrasting

confidence: 53%

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Ablation of a galectin preferentially expressed in adipocytes increases lipolysis, reduces adiposity, and improves insulin sensitivity in mice

Yang

Graham

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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The breakdown of triglycerides, or lipolysis, is a tightly controlled process that regulates fat mobilization in accord with an animal's energy needs. It is well established that lipolysis is stimulated by hormones that signal energy demand and is suppressed by the antilipolytic hormone insulin. However, much still remains to be learned about regulation of lipolysis by intracellular signaling pathways in adipocytes. Here we show that galectin-12, a member of a β-galactosidebinding lectin family preferentially expressed by adipocytes, functions as an intrinsic negative regulator of lipolysis. Galectin-12 is primarily localized on lipid droplets and regulates lipolytic protein kinase A signaling by acting upstream of phosphodiesterase activity to control cAMP levels. Ablation of galectin-12 in mice results in increased adipocyte mitochondrial respiration, reduced adiposity, and ameliorated insulin resistance/glucose intolerance. This study identifies unique properties of this intracellular galectin that is localized to an organelle and performs a critical function in lipid metabolism. These findings add to the significant functions exhibited by intracellular galectins, and have important therapeutic implications for human metabolic disorders. obesity | energy metabolism | diabetes

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Section: Discussioncontrasting

confidence: 53%

“…An early report suggested that galectin-12 is involved in adipogenesis in vitro (15). However, we did not observe major alterations in the expression of several adipose genes examined in Lgals12 −/− mice, suggesting that adipose tissue development in these mice are largely normal ( Fig.…”

Section: Galectin-12 Ablation Reduces Adiposity Associated With Decrecontrasting

confidence: 38%

Ablation of a galectin preferentially expressed in adipocytes increases lipolysis, reduces adiposity, and improves insulin sensitivity in mice

Yang

Graham

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Galectins are a family of carbohydrate-binding proteins (lectins) (Cooper, 2002). Recently galectin-12 has been attributed several key roles in adipocyte physiology such as being an intrinsic negative regulator of lipolysis and a responsive gene to antidiabetic thizolidinedione (TZD) treatment (Hotta et al, 2001;Yang et al, 2004Yang et al, , 2009). These findings have lead to hypothesize that galectin-12 may improve insulin sensitivity after TZD treatment, at least partially via induction of apoptosis of preferentially large insulin-resistant adipocytes (Hotta et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Modulation of white adipose tissue proteome by aging and calorie restriction

et al. 2010

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SummaryAging is associated with an accrual of body fat, progressive development of insulin resistance and other obesity comorbidities that contribute to decrease life span. Caloric restriction (CR), which primarily affects energy stores in adipose tissue, is known to extend life span and retard the aging process in animal models. In this study, a proteomic approach combining 2-DE and MS was used to identify proteins modulated by aging and CR in rat white adipose tissue proteome. Proteomic analysis revealed 133 differentially expressed spots, 57 of which were unambiguously identified by MS. Although CR opposed part of the age-associated protein expression patterns, many effects of CR were on proteins unaltered by age, suggesting that the effects of CR on adipose tissue are only weakly related to those of aging. Particularly, CR and aging altered glucose, intermediate and lipid metabolism, with CR enhancing the expression of enzymes involved in oxalacetate and NADPH production, lipid biosynthesis and lipolysis. Consistently, insulin-b and b3-adrenergic receptors were also increased by CR, which denotes improved sensitivity to lipogenic ⁄ lipolytic stimuli. Other beneficial outcomes of CR were an improvement in oxidative stress, preventing the age-associated decrease in several antioxidant enzymes. Proteins involved in cytoskeleton, iron storage, energy metabolism and several proteins with novel or unknown functions in adipose tissue were also modulated by age and ⁄ or CR. Such orchestrated changes in expression of multiple proteins provide insights into the mechanism underlying CR effects, ultimately allowing the discovery of new markers of aging and targets for the development of CR-mimetics.

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“…However, except for one paper in 2004 suggesting that galectin-12 regulated preadipocyte differentiation (9), the function of galectin-12 remained unknown. Now, the work by Yang et al (6) shows that galectin-12 localizes to lipid droplets in adipocytes.…”

Section: Galectins In Adipocytesmentioning

confidence: 99%

Burn control, an adipocyte-specific function for galectin-12

Baum

2011

Proc. Natl. Acad. Sci. U.S.A.

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Galectin-12 Is Required for Adipogenic Signaling and Adipocyte Differentiation

Cited by 69 publications

References 70 publications

Ablation of a galectin preferentially expressed in adipocytes increases lipolysis, reduces adiposity, and improves insulin sensitivity in mice

Ablation of a galectin preferentially expressed in adipocytes increases lipolysis, reduces adiposity, and improves insulin sensitivity in mice

Modulation of white adipose tissue proteome by aging and calorie restriction

Burn control, an adipocyte-specific function for galectin-12

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