Lipocalin‐2 expression and serum levels as early predictors of type 2 diabetes mellitus in obese women

Rashad, Nearmeen M.; El‐Shal, Amal S.; Etewa, Rasha L.; Wadea, Fady M.

doi:10.1002/iub.1594

Cited by 33 publications

(26 citation statements)

References 36 publications

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“…This type of compensatory homeostatic response most probably accounts for the elevated circulating LCN2 levels that have been reported in obese and insulin-resistant states in mice and humans (De la Chesnaye et al, 2015;Wang et al, 2007Wang et al, , 2018Zhang et al, 2008;Yan et al, 2007;Rashad et al, 2017;Garbacz et al, 2017). Indeed, we found elevated circulating LCN2 levels in obese, prediabetic patients that correlate with BMI and insulin resistance but also β-cell function, indices of healthy glucose metabolism.…”

Section: Discussionsupporting

confidence: 72%

“…In addition, normal-weight women whose LCN2 serum levels positively correlate with energy expenditure after a high-fat meal have improved fatty acid oxidation (Paton et al, 2013). Contrasting with this evidence, we note that elevated LCN2 serum levels have been associated with obesity and insulin resistance in mouse models and humans (Yan et al, 2007;Zhang et al, 2008;Wang et al, 2007;Kanaka-Gantenbein et al, 2008;Yoo et al, 2014;Rashad et al, 2017). Whether this increase in LCN2 levels is a cause or result of the metabolic dysregulation and whether it has an impact on disease progression have not been examined.…”

Section: Introductionmentioning

confidence: 86%

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Lipocalin-2 counteracts metabolic dysregulation in obesity and diabetes

Mosialou

Shikhel

Luo

et al. 2020

Journal of Experimental Medicine

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Regulation of food intake is a recently identified endocrine function of bone that is mediated by Lipocalin-2 (LCN2). Osteoblast-secreted LCN2 suppresses appetite and decreases fat mass while improving glucose metabolism. We now show that serum LCN2 levels correlate with insulin levels and β-cell function, indices of healthy glucose metabolism, in obese mice and obese, prediabetic women. However, LCN2 serum levels also correlate with body mass index and insulin resistance in the same individuals and are increased in obese mice. To dissect this apparent discrepancy, we modulated LCN2 levels in mice. Silencing Lcn2 expression worsens metabolic dysfunction in genetic and diet-induced obese mice. Conversely, increasing circulating LCN2 levels improves metabolic parameters and promotes β-cell function in mouse models of β-cell failure acting as a growth factor necessary for β-cell adaptation to higher metabolic load. These results indicate that LCN2 up-regulation is a protective mechanism to counteract obesity-induced glucose intolerance by decreasing food intake and promoting adaptive β-cell proliferation.

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Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 86%

Lipocalin-2 counteracts metabolic dysregulation in obesity and diabetes

Mosialou

Shikhel

Luo

et al. 2020

Journal of Experimental Medicine

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“…Moreover, elevated serum LCN2 level was shown to be associated with increased risk for T2DM. A recent study also indicated that LCN2 levels were elevated in obese women and could be used as an early predictor of T2DM [13]. Nevertheless, no significant association of LCN2 with HOMA-IR was indicated in non-diabetic obese women [14].…”

Section: Introductionmentioning

confidence: 99%

Podwyższone stężenia lipokaliny-2 w surowicy krwi są związane ze wskaźnikami metabolizmu glukozy i metabolizmu kostnego w przebiegu cukrzycy typu 2

Wang¹,

Ye²,

Qian³

et al. 2018

Endokrynologia Polska

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Elevated serum lipocalin 2 levels are associated with indexes of both glucose and bone metabolism in type 2 diabetes mellitusPodwyższone stężenia lipokaliny-2 w surowicy krwi są związane ze wskaźnikami metabolizmu glukozy i metabolizmu kostnego w przebiegu cukrzycy typu 2 AbstractIntroduction: The role of lipocalin 2 (LCN2) in type 2 diabetes mellitus (T2DM) needs to be fully elucidated. Moreover, bone has been demonstrated to modulate glucose metabolism via LCN2. We thus performed this study to investigate the association of LCN2 with indexes of glucose metabolism in T2DM. The associations of LCN2 with bone metabolism were examined concurrently. Material and methods: A total of 288 Chinese Han subjects entered in this study, including 146 patients with T2DM and 142 subjects with normal glucose tolerance. Insulin resistance was assessed by HOMA-IR, and b-cell function was assessed by HOMA-b. For patients with T2DM, bone turnover markers, type 1 N-terminal procollagen, and collagen type 1 cross-linked C-telopeptide were assayed, and bone mineral density (BMD) of the lumbar spine and femoral neck were measured. Results: Serum LCN2 levels in T2DM were higher than those in subjects with normal glucose tolerance (p = 0.005). Moreover, LCN2 was positively associated with fasting serum insulin (r = 0.262, p = 0.001), HOMA-IR (r = 0.185, p = 0.026), and HOMA-b (r = 0.306, p < 0.001), respectively, and negatively associated with fasting plasma glucose (r = -0.218, p = 0.006). Additionally, femoral neck BMD (b = -0.176, p = 0.033), type 1 N-terminal procollagen (b = 0.181, p = 0.026), and collagen type 1 cross-linked C-telopeptide (b = -0.168, p = 0.037) were independent predictors for LCN2 in T2DM. Conclusions: LCN2 was associated with indexes of glucose metabolism. Furthermore, BMD and bone turnover markers were independent predictors for LCN2 in T2DM. We speculate that LCN2 might play a role in the cross-talk between bone homeostasis and glucose homeostasis. (Endokrynol Pol 2018; 69 (3): 276-282)

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“…Postprandial serum levels of LCN2 were significantly increased after high‐fat meals; furthermore, this increase in postprandial LCN2 levels was accompanied by enhanced total energy expenditure, but only in normal‐weight individuals . In obese subjects, a decrease in postprandial LCN2 concentration occurred rather than an increase, and this decrease was generally attributed to higher levels of serum LCN2 under basal states in obesity . The underlying mechanisms that would account for these differences are unclear.…”

Section: Osteoblast‐derived Lcn2 As An Appetite Suppressormentioning

confidence: 99%

“…67 In obese subjects, a decrease in postprandial LCN2 concentration occurred rather than an increase, 67 and this decrease was generally attributed to higher levels of serum LCN2 under basal states in obesity. 68 The underlying mechanisms that would account for these differences are unclear. Whether Mechanistically, LCN2 can cross the blood-brain barrier, bind to the melanocortin 4 receptor (MC4R) in the paraventricular nucleus and ventromedial neurons of the hypothalamus, and use an established MC4R-dependent anorexia-promoting pathway to exert its anorexigenic function, thus decreasing body weight and fat mass and improving insulin sensitivity 10 (Figure 1).…”

Section: Osteoblast-derived Lcn2 As An Appetite Suppressormentioning

confidence: 99%

Bone: Another potential target to treat, prevent and predict diabetes

Liu¹,

Mosialou

Liu

2018

Diabetes Obesity Metabolism

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Type 2 diabetes mellitus is now a worldwide health problem with increasing prevalence. Mounting efforts have been made to treat, prevent and predict this chronic disease. In recent years, increasing evidence from mice and clinical studies suggests that bone-derived molecules modulate glucose metabolism. This review aims to summarize our current understanding of the interplay between bone and glucose metabolism and to highlight potential new means of therapeutic intervention. The first molecule recognized as a link between bone and glucose metabolism is osteocalcin (OCN), which functions in its active form, that is, undercarboxylated OCN (ucOC). ucOC acts in promoting insulin expression and secretion, facilitating insulin sensitivity, and favouring glucose and fatty acid uptake and utilization. A second bone-derived molecule, lipocalin2, functions in suppressing appetite in mice through its action on the hypothalamus. Osteocytes, the most abundant cells in bone matrix, are suggested to act on the browning of white adipose tissue and energy expenditure through secretion of bone morphogenetic protein 7 and sclerostin. The involvement of bone resorption in glucose homeostasis has also been examined. However, there is evidence indicating the implication of the receptor activator of nuclear factor κ-B ligand, neuropeptide Y, and other known and unidentified bone-derived factors that function in glucose homeostasis. We summarize recent advances and the rationale for treating, preventing and predicting diabetes by skeleton intervention.

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Lipocalin‐2 expression and serum levels as early predictors of type 2 diabetes mellitus in obese women

Cited by 33 publications

References 36 publications

Lipocalin-2 counteracts metabolic dysregulation in obesity and diabetes

Lipocalin-2 counteracts metabolic dysregulation in obesity and diabetes

Podwyższone stężenia lipokaliny-2 w surowicy krwi są związane ze wskaźnikami metabolizmu glukozy i metabolizmu kostnego w przebiegu cukrzycy typu 2

Bone: Another potential target to treat, prevent and predict diabetes

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