Zinc alpha2 glycoprotein protects against obesity-induced hepatic steatosis

Xiao, Xinhua; Wang, Yadi; Qi, Xiaoyan; Wang, Yuan‐Yuan; Li, Jiaoyang; Han, Li; Zhang, Pei-Ying; Hailin, Liao; Li, Meihua; Liao, Zhe-Zhen; Yang, Jing; Xu, Chenghai; Ge, Wen; Liu, Jianghua

doi:10.1038/s41366-018-0151-9

Cited by 27 publications

(36 citation statements)

References 51 publications

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“…The baseline characteristics of the cohort with normoalbuminuria (n=341) are shown in Table 1. The participants, of whom 52% were men, had a mean age of 57AE10 years and a median (IQR) diabetes duration of 8 (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) years. Baseline eGFR levels were progressively reduced as ZAG tertile increased.…”

Section: Resultsmentioning

confidence: 99%

“…The molecule functions as a lipid-mobilizing factor that stimulates lipolysis in adipocytes, contributing to weight loss and associated cancer cachexia [9]. Studies in humans and animal models have suggested a protective role of ZAG against obesity, insulin resistance, hepatic steatosis, and inflammation [10][11][12]. Contradictorily, ZAG protein expression was found to be upregulated in the white adipose tissue of people and mice with CKD [13].…”

Section: Introductionmentioning

confidence: 99%

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Zinc‐α2‐glycoprotein is associated with non‐albuminuric chronic kidney disease progression in type 2 diabetes: a retrospective study with 4‐year follow‐up

et al. 2020

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Aim To investigate the association between baseline plasma zinc-a2-glycoprotein and non-albuminuric chronic kidney disease progression in type 2 diabetes. Methods Adults with normoalbuminuria at entry (n=341; age 57AE10 years, 52% men) were analysed. Chronic kidney disease progression was defined as a decrease in chronic kidney disease stage and a decline of ≥25% in estimated GFR from baseline. Baseline plasma zinc-a2-glycoprotein levels were quantified by immunoassay, and analysed either as a continuous variable or by tertiles in Cox proportional hazards models. Model discrimination was assessed using Harrell's C-index. A sensitivity analysis was performed on a subset of individuals who maintained normoalbuminuria during follow-up. Results Chronic kidney disease progression occurred in 54 participants (16%). Zinc-a2-glycoprotein levels were elevated in chronic kidney disease progressors (P = 0.011), and more progressors were assigned to the higher zinc-a2glycoprotein tertile than non-progressors. In the unadjusted Cox model, zinc-a2-glycoprotein, both as a continuous variable (hazard ratio 1.72, 95% CI 1.08-2.75) and tertile 3 (vs tertile 1; hazard ratio 2.14, 95% CI 1.10-4.17), predicted chronic kidney disease progression. The association persisted after multivariable adjustment. The C-index of the Cox model increased significantly after incorporation of zinc-a2-glycoprotein into a base model comprising reninangiotensin system antagonist usage. Sensitivity analysis showed that zinc-a2-glycoprotein independently predicted chronic kidney disease progression among individuals who maintained normoalbuminuria during follow-up. Conclusions Plasma zinc-a2-glycoprotein is associated with chronic kidney disease progression, and may serve as a useful early biomarker for predicting non-albuminuric chronic kidney disease progression in type 2 diabetes.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Zinc‐α2‐glycoprotein is associated with non‐albuminuric chronic kidney disease progression in type 2 diabetes: a retrospective study with 4‐year follow‐up

et al. 2020

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“…Additionally, one study showed that the overexpression of ZAG alleviated HFD-induced IR and decreased the lipid contents of muscles in mice [22]. Another study showed that ZAG overexpression could protect against nonalcoholic fatty liver disease (NAFLD) in vivo or in vitro by ameliorating hepatic steatosis, IR, and inflammation [23]. Therefore, we speculated that decreased ZAG levels in obese and IR subjects potentially occur to offset IR-induced metabolic stress.…”

Section: Discussionmentioning

confidence: 97%

Association between circulating zinc-α2-glycoprotein levels and the different phenotypes of polycystic ovary syndrome

Tang

et al. 2020

Endocr J

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Polycystic ovary syndrome (PCOS) diagnosis combines various clinical phenotypes. The definition of PCOS is still controversial because insulin resistance (IR) and dysmetabolism do not constitute PCOS diagnostic criteria. We analyzed whether a circulating biomarker zinc-α2-glycoprotein (ZAG) related to IR and metabolic dysfunction can predict PCOS phenotypes. We then recruited 100 PCOS patients and 99 healthy women as the control group to assess the relationship between ZAG and metabolic characteristics. The euglycemic-hyperinsulinemic clamp helped assess insulin sensitivity, and the enzyme immunometric assay was deployed for ZAG levels. Our PCOS cohort presented sixty-nine patients with hyperandrogenism, eighty-six patients with chronic oligoanovulation, and eighty-one patients with polycystic ovaries by ultrasonographic evaluation. Additionally, the circulating ZAG levels were considerably reduced in all PCOS patients compared with healthy women (p < 0.05 or p < 0.01). Additionally, sixty-nine PCOS patients had IR, and circulating ZAG levels were also different among the phenotypes. Furthermore, the normoandrogenic type specifically exhibited the highest circulating ZAG levels among all PCOS phenotypes (p < 0.05 or p < 0.01). Additionally, normoandrogenic phenotype patients had reduced HOMA-IR scores and greater M-values than those in the classic phenotypes (p < 0.05). The circulating ZAG levels, however, were not associated with oligoanovulation but were correlated with hyperandrogenism and PCO morphology. In summary, circulating ZAG levels serve as suitable PCOS phenotype biomarkers, aiding physicians to identify women who merit screening.

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“…Insulin receptor substrate-1 (IRs-1) is a core factor in insulin signaling transduction. Research showed that phosphorylation of IRs-1 at Ser accounts for IR, while phosphorylation of IRs-1 at Tyr is required for responses of insulin stimulates (Bhattacharyya et al 2015;Xiao et al 2018) . In metabolic disorders, such as NAFLD and T2DM, impaired IRs-1 level was observed, for instance, lipid accumulation in the liver was closely associated with increased serine phosphorylation of IRs-1 (Araujo et al 2018;Dallak 2018;Dong et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Peer Review #1 of "Polyphenol-rich Trapa quadrispinosa pericarp extract ameliorates high-fat diet induced non-alcoholic fatty liver disease by regulating lipid metabolism and insulin resistance in mice (v0.2)"

Fernándes¹

2019

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In China, Trapa quadrispinosa (also called water caltrop) has long been used as a function food and folk medicine to treat diabetes mellitus for years. In the present study, the extract of T. quadrispinosa pericarp (TQPE) which mainly contains hydrolysable tannins was prepared to investigate the potential therapeutic action in non-alcoholic fatty liver disease (NAFLD) mice induced by high fat-diet (HFD). After the administration of TQPE (15, 30 mg/kg/day) for 8 weeks, the increased weight of body and liver were significantly suppressed. TQPE also ameliorated liver lipid deposition and reduced lipids parameters of blood in mice. Moreover, TQPE attenuated oxidative stress and showed a hepatoprotective effect in mice. TQPE was also found to decrease the value of homeostatic model assessment for insulin resistance. In addition, TQPE administration increased the phosphorylation of AMP-activated protein kinase (AMPK) and Acetyl-CoA carboxylase (ACC) and inhibited sterol regulatory element-binding protein (SREBP) in the liver tissue. Meanwhile, TQPE elevated insulin receptor substrate-1 (IRs-1) and protein kinase B (Akt) phosphorylation. These results reflected that, as a nature product, TQPE is a potential agent for suppressing the process of NAFLD via regulation of the AMPK/SREBP/ACC and IRs-1/Akt pathways.

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Zinc alpha2 glycoprotein protects against obesity-induced hepatic steatosis

Abstract: Our results revealed that ZAG could protect against NAFLD by ameliorating hepatic steatosis, IR, and inflammation.

Cited by 27 publications

References 51 publications

Zinc‐α2‐glycoprotein is associated with non‐albuminuric chronic kidney disease progression in type 2 diabetes: a retrospective study with 4‐year follow‐up

Zinc‐α2‐glycoprotein is associated with non‐albuminuric chronic kidney disease progression in type 2 diabetes: a retrospective study with 4‐year follow‐up

Association between circulating zinc-α2-glycoprotein levels and the different phenotypes of polycystic ovary syndrome

Peer Review #1 of "Polyphenol-rich Trapa quadrispinosa pericarp extract ameliorates high-fat diet induced non-alcoholic fatty liver disease by regulating lipid metabolism and insulin resistance in mice (v0.2)"

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