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Theranostics 2023; 13(11):3550-3567. doi:10.7150/thno.82697 This issue Cite

Research Paper

Label-free optical metabolic imaging of adipose tissues for prediabetes diagnosis

Liping Chen^1,2, Guihui Qin^1,2, Yuhong Liu³, Moxin Li^1,2, Yue Li^1,2, Lun-Zhang Guo⁴, Lidong Du^1,2, Weiming Zheng⁵, Pei-Chun Wu^1,6, Yueh-Hsun Chuang⁷, Xiaoyan Wang^1,2✉, Tzung-Dau Wang^8✉, Ja-An Annie Ho^6✉, Tzu-Ming Liu^1,2✉

1. Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macao SAR, China.
2. MOE Frontiers Science Center for Precision Oncology, University of Macau, Macao SAR, China.
3. School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
4. Institute of Biomedical Engineering, National Taiwan University, Taipei 10617, Taiwan.
5. Translational Medicine R&D Center, Zhuhai UM Science and Technology Research Institute, Zhuhai, China.
6. Department of Biochemical Science & Technology, National Taiwan University, Taipei 10617, Taiwan.
7. Department of Anesthesiology, National Taiwan University Hospital and College of Medicine, Taipei 10002, Taiwan.
8. Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei 10002, Taiwan.

✉ Corresponding authors: Tzu-Ming Liu, tmliuedu.mo; Ja-An Annie Ho, jahoedu.tw; Tzung-Dau Wang, tdwangedu.tw; Xiaoyan Wang, xiaoyanwang85com. Address: Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macao SAR, China. TEL: +853-8822-4693. More

Abstract

Rationale: Prediabetes can be reversed through lifestyle intervention, but its main pathologic hallmark, insulin resistance (IR), cannot be detected as conveniently as blood glucose testing. In consequence, the diagnosis of prediabetes is often delayed until patients have hyperglycemia. Therefore, developing a less invasive diagnostic method for rapid IR evaluation will contribute to the prognosis of prediabetes. Adipose tissue is an endocrine organ that plays a crucial role in the development and progression of prediabetes. Label-free visualizing the prediabetic microenvironment of adipose tissues provides a less invasive alternative for the characterization of IR and inflammatory pathology.

Methods: Here, we successfully identified the differentiable features of prediabetic adipose tissues by employing the metabolic imaging of three endogenous fluorophores NAD(P)H, FAD, and lipofuscin-like pigments.

Results: We discovered that 1040-nm excited lipofuscin-like autofluorescence could mark the location of macrophages. This unique feature helps separate the metabolic fluorescence signals of macrophages from those of adipocytes. In prediabetes fat tissues with IR, we found only adipocytes exhibited a low redox ratio of metabolic fluorescence and high free NAD(P)H fraction a₁. This differential signature disappears for mice who quit the high-fat diet or high-fat-high-sucrose diet and recover from IR. When mice have diabetic hyperglycemia and inflamed fat tissues, both adipocytes and macrophages possess this kind of metabolic change. As confirmed with RNA-seq analysis and histopathology evidence, the change in adipocyte's metabolic fluorescence could be an indicator or risk factor of prediabetic IR.

Conclusion: Our study provides an innovative approach to diagnosing prediabetes, which sheds light on the strategy for diabetes prevention.

Keywords: prediabetes, adipose tissue, redox ratio, NAD(P)H fluorescence lifetime, lipofuscin-like fluorescence

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