. 2024 Feb 6;36(2):438-453.e6.

doi: 10.1016/j.cmet.2024.01.003.

Region-specific transcriptomic responses to obesity and diabetes in macaque hypothalamus

Ying Lei¹, Xian Liang², Yunong Sun¹, Ting Yao³, Hongyu Gong⁴, Zhenhua Chen⁵, Yuanqing Gao⁶, Hui Wang⁷, Ru Wang⁸, Yunqi Huang¹, Tao Yang⁹, Miao Yu⁷, Longqi Liu¹, Chun-Xia Yi¹⁰, Qing-Feng Wu⁵, Xingxing Kong¹¹, Xun Xu¹², Shiping Liu¹³, Zhi Zhang¹⁴, Tiemin Liu¹⁵

Affiliations

¹ BGI-Research, Hangzhou 310012, China; BGI-Research, Shenzhen 518103, China.
² State Key Laboratory of Genetic Engineering, Department of Endocrinology and Metabolism, Human Phenome Institute, Institute of Metabolism and Integrative Biology, and School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200438, China; School of Life Sciences, Fudan University, Shanghai 200438, China.
³ Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University School of Medicine, Xi'an, Shanxi 710063, China.
⁴ School of Life Sciences, Institues of Biomedical Sciences, Inner Mongolia University, Hohhot 010000, China.
⁵ State Key Laboratory of Molecular Development Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
⁶ Jiangsu Provincial Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
⁷ School of Life Sciences, Fudan University, Shanghai 200438, China.
⁸ School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China.
⁹ China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China.
¹⁰ Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands.
¹¹ School of Life Sciences, Fudan University, Shanghai 200438, China. Electronic address: kongxingxing@fudan.edu.cn.
¹² BGI-Research, Hangzhou 310012, China; BGI-Research, Shenzhen 518103, China. Electronic address: xuxun@genomics.cn.
¹³ BGI-Research, Hangzhou 310012, China; BGI-Research, Shenzhen 518103, China. Electronic address: liushiping@genomics.cn.
¹⁴ State Key Laboratory of Genetic Engineering, Department of Endocrinology and Metabolism, Human Phenome Institute, Institute of Metabolism and Integrative Biology, and School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200438, China; School of Life Sciences, Fudan University, Shanghai 200438, China. Electronic address: z_zhang@fudan.edu.cn.
¹⁵ State Key Laboratory of Genetic Engineering, Department of Endocrinology and Metabolism, Human Phenome Institute, Institute of Metabolism and Integrative Biology, and School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200438, China; School of Life Sciences, Fudan University, Shanghai 200438, China; School of Life Sciences, Institues of Biomedical Sciences, Inner Mongolia University, Hohhot 010000, China. Electronic address: tiemin_liu@fudan.edu.cn.

PMID: 38325338
DOI: 10.1016/j.cmet.2024.01.003

Free article

Region-specific transcriptomic responses to obesity and diabetes in macaque hypothalamus

Ying Lei et al. Cell Metab. 2024.

Free article

. 2024 Feb 6;36(2):438-453.e6.

doi: 10.1016/j.cmet.2024.01.003.

Authors

Affiliations

¹ BGI-Research, Hangzhou 310012, China; BGI-Research, Shenzhen 518103, China.
² State Key Laboratory of Genetic Engineering, Department of Endocrinology and Metabolism, Human Phenome Institute, Institute of Metabolism and Integrative Biology, and School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200438, China; School of Life Sciences, Fudan University, Shanghai 200438, China.
³ Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University School of Medicine, Xi'an, Shanxi 710063, China.
⁴ School of Life Sciences, Institues of Biomedical Sciences, Inner Mongolia University, Hohhot 010000, China.
⁵ State Key Laboratory of Molecular Development Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
⁶ Jiangsu Provincial Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
⁷ School of Life Sciences, Fudan University, Shanghai 200438, China.
⁸ School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China.
⁹ China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China.
¹⁰ Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands.
¹¹ School of Life Sciences, Fudan University, Shanghai 200438, China. Electronic address: kongxingxing@fudan.edu.cn.
¹² BGI-Research, Hangzhou 310012, China; BGI-Research, Shenzhen 518103, China. Electronic address: xuxun@genomics.cn.
¹³ BGI-Research, Hangzhou 310012, China; BGI-Research, Shenzhen 518103, China. Electronic address: liushiping@genomics.cn.
¹⁴ State Key Laboratory of Genetic Engineering, Department of Endocrinology and Metabolism, Human Phenome Institute, Institute of Metabolism and Integrative Biology, and School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200438, China; School of Life Sciences, Fudan University, Shanghai 200438, China. Electronic address: z_zhang@fudan.edu.cn.
¹⁵ State Key Laboratory of Genetic Engineering, Department of Endocrinology and Metabolism, Human Phenome Institute, Institute of Metabolism and Integrative Biology, and School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200438, China; School of Life Sciences, Fudan University, Shanghai 200438, China; School of Life Sciences, Institues of Biomedical Sciences, Inner Mongolia University, Hohhot 010000, China. Electronic address: tiemin_liu@fudan.edu.cn.

PMID: 38325338
DOI: 10.1016/j.cmet.2024.01.003

Abstract

The hypothalamus plays a crucial role in the progression of obesity and diabetes; however, its structural complexity and cellular heterogeneity impede targeted treatments. Here, we profiled the single-cell and spatial transcriptome of the hypothalamus in obese and sporadic type 2 diabetic macaques, revealing primate-specific distributions of clusters and genes as well as spatial region, cell-type-, and gene-feature-specific changes. The infundibular (INF) and paraventricular nuclei (PVN) are most susceptible to metabolic disruption, with the PVN being more sensitive to diabetes. In the INF, obesity results in reduced synaptic plasticity and energy sensing capability, whereas diabetes involves molecular reprogramming associated with impaired tanycytic barriers, activated microglia, and neuronal inflammatory response. In the PVN, cellular metabolism and neural activity are suppressed in diabetic macaques. Spatial transcriptomic data reveal microglia's preference for the parenchyma over the third ventricle in diabetes. Our findings provide a comprehensive view of molecular changes associated with obesity and diabetes.

Keywords: Stereo-seq; diabetes; energy metabolism; hypothalamus; microglia; monkey; neurotensin; obesity; oxytocin; single-nucleus RNA sequencing.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- Elsevier Science
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Region-specific transcriptomic responses to obesity and diabetes in macaque hypothalamus

Affiliations

Region-specific transcriptomic responses to obesity and diabetes in macaque hypothalamus

Authors

Affiliations

Abstract

Conflict of interest statement

Similar articles

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical

Abstract

Conflict of interest statement

Similar articles

Publication types

MeSH terms

Related information

LinkOut - more resources

Full Text Sources

Medical