Nobuyo Maeda

· Professor

University of North Carolina at Chapel Hill · Nutrition

Active 1974–2025

h-index97

Citations34.6k

Papers3878 last 5y

Funding$48.4M2 active

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About

Nobuyo Maeda, PhD, is a professor in the Department of Nutrition at UNC Gillings School of Global Public Health. Her research projects focus on understanding gene-gene and gene-environment interactions in complex human diseases such as atherosclerosis, hypertension, and diabetes. She has been involved in generating mice carrying mutations in genes related to lipid metabolism using homologous recombination in embryonic stem cells to better understand hypercholesterolemia's role in atherogenesis. One of her notable contributions includes the development of apoE-deficient mice in 1992, which develop high cholesterol and atherosclerotic lesions similar to those in humans. Her laboratory studies how genetic factors, including those involved in blood pressure regulation, inflammation, and glucose metabolism, along with dietary factors like fat and antioxidant vitamins, influence the progression of atherosclerotic lesions. Dr. Maeda received the Method to Extend Research in Time (MERIT) Award from the National Heart, Lung and Blood Institute in 1998.

Research topics

Biology
Neuroscience
Medicine
Computer Science
Psychology
Pharmacology
Cell biology
Biochemistry
Genetics
Internal medicine
Immunology
Pathology

Selected publications

Vitamin B12 Protects Against Early Diabetic Kidney Injury and Alters Clock Gene Expression in Mice
Biomolecules · 2025-12-03
articleOpen accessSenior author
Vitamin B12 (B12) is a strong antioxidant and a cofactor for methionine synthase supporting DNA/RNA/protein methylation. We previously demonstrated that oral high-dose B12 supplement mitigates diabetic cardiomyopathy in Akita diabetic mice expressing twice the normal levels of Elmo1 (Engulfment and cell motility 1). To assess how B12 prevents early kidney damage, we treated Elmo1HH mice and diabetic Elmo1HH Ins2Akita/+ mice with or without B12 in drinking water starting at 8 weeks of age. At 16 weeks, markedly reduced mesangial expansion was detected in the B12-treated diabetic kidneys (22% of glomeruli affected vs. 70% in the untreated diabetic kidneys). RNAseq analysis of the kidneys revealed that B12 suppressed expression of genes for adaptive immune response, while it upregulated those for solute carrier transporters and antioxidant genes. Strikingly, B12 treatment suppressed activators of circadian rhythm, Clock and Bmal1, and upregulated repressors like Cry1/2, Per1-3 and Dbp, suggesting a shift in their rhythmicity. B12 also upregulated linker histone H1 variants, and enhanced chromatin stability and cell cycle regulation. In BU.MPT proximal tubular cells in culture, B12 shifted forward the circadian expression phase of Bmal1 and Per1. Taken together, B12 supplement effectively mitigates early development of diabetic nephropathy in diabetic mice, potentially involving regulation of circadian rhythm.
Publisher OA PDF DOI
Corrigendum: Absolute winding number differentiates mouse spatial navigation strategies with genetic risk for Alzheimer's disease
UNC Libraries · 2025-04-30
articleOpen access1st authorCorresponding
[This corrects the article DOI: 10.3389/fnins.2022.848654.].
Publisher DOI
Impacts of Metabolic Reprogramming on the Onset of Diabetic Nephropathy in Mice with Varied Lias Gene Expression Levels
2025-07-15
preprint
Metabolic and energy reprogramming, potentially regulated by protein lipoylation, plays a critical role in maintaining kidney function and cell survival in diabetic kidney disease (DKD). However, it remains unclear whether improper reprogramming contributes to the onset of DKD. To investigate this issue, we developed a group of metabolic mouse models with varying levels of protein lipoylation, which resulted from distinct gene expression levels of lipoic acid synthase (Lias), and corresponding metabolic activities. Lias synthesizes α-lipoic acid, which can regulate mitochondrial function. We crossed these Lias metabolic models with Ins2Akita/+ mice, a commonly used type 1 diabetes (T1D) model that also exhibits T2D phenotype. These models allow us to investigate the role of reprogramming and its regulation by protein lipoylation in initiating DKD.LiasH/HIns2Akita/+ mice, which had a high metabolic activity associated with increased protein lipoylation levels, exhibited milder pathological changes than LiasL/LIns2Akita/+ and Lias+/+Ins2Akita/+ mice at the early stages of DKD. These changes included reduced microalbuminuria, less expansion of the glomerular mesangial matrix, and decreased mitochondrial damage in proximal tubular epithelial cells. However, the beneficial effect was reduced in Lias gene knockdown, specifically within podocytes of LiasH/HIns2Akita/+ mice, achieved using a Cre-LoxP system. The finding confirms that the increased protein lipoylation in podocytes helps attenuate DKD.Our study demonstrates that elevated protein lipoylation mitigates the early stages of DKD by influencing metabolic and energy reprogramming. This finding may offer a potential new strategy for preventing and treating DKD initiation.
Publisher DOI
Vitamin B12 Modulates Circadian Clock Genes and Protects Early Diabetic Kidney Injury
Preprints.org · 2025-10-13
preprintOpen accessSenior author
Vitamin B12 (B12) is a co-factor for methionine synthase and supports DNA/RNA/protein methylation through S-adenosylmethionine production. We previously demonstrated that oral high-dose B12 supplement mitigates diabetic complications in Akita diabetic Elmo1H/H mice, which express twice normal levels of Elmo1 (Engulfment and Cell Motility 1) that enhance diabetic complications. To assess how B12 prevents early stage of kidney damage, we treated nondiabetic and Akita diabetic Elmo1H/H mice with or without B12 in drinking water, starting at 8 weeks old. At 16 weeks, mesangial expansion in untreated diabetic kidneys began, but peritubular fibrosis and inflammatory cell accumulation were minimal. B12-treated diabetic kidneys were essentially normal. RNAseq analysis of the kidneys revealed B12 suppressed expression of genes for adaptive immune response, while upregulated those for solute carrier transporters. Importantly, B12 modulated circadian genes independently of diabetic status: B12 suppressed Clock, Bmal1, and Npas2, while upregulated Cry1/2, Per1–3, Nr1d2, and Dbp. B12 treatment significantly upregulated linker histone H1 variants, suggesting enhanced chromatin stability and transcriptional regulation. In BU.MPT cells, B12 advanced peaks of Bmal1 and Per1, but delayed Cry1, indicating shortened circadian rhythm. As conclusion, B12 supplement effectively mitigates early development of diabetic nephropathy, likely involving regulation of circadian genes and linker H1 regulation.
Publisher OA PDF DOI
Impacts of Metabolic Reprogramming on the Onset of Diabetic Nephropathy in Mice with Varied Lias Gene Expression Levels
2025-07-15
preprintOpen access
Metabolic and energy reprogramming, potentially regulated by protein lipoylation, plays a critical role in maintaining kidney function and cell survival in diabetic kidney disease (DKD). However, it remains unclear whether improper reprogramming contributes to the onset of DKD. To investigate this issue, we developed a group of metabolic mouse models with varying levels of protein lipoylation, which resulted from distinct gene expression levels of lipoic acid synthase (Lias), and corresponding metabolic activities. Lias synthesizes α-lipoic acid, which can regulate mitochondrial function. We crossed these Lias metabolic models with Ins2Akita/+ mice, a commonly used type 1 diabetes (T1D) model that also exhibits T2D phenotype. These models allow us to investigate the role of reprogramming and its regulation by protein lipoylation in initiating DKD.LiasH/HIns2Akita/+ mice, which had a high metabolic activity associated with increased protein lipoylation levels, exhibited milder pathological changes than LiasL/LIns2Akita/+ and Lias+/+Ins2Akita/+ mice at the early stages of DKD. These changes included reduced microalbuminuria, less expansion of the glomerular mesangial matrix, and decreased mitochondrial damage in proximal tubular epithelial cells. However, the beneficial effect was reduced in Lias gene knockdown, specifically within podocytes of LiasH/HIns2Akita/+ mice, achieved using a Cre-LoxP system. The finding confirms that the increased protein lipoylation in podocytes helps attenuate DKD.Our study demonstrates that elevated protein lipoylation mitigates the early stages of DKD by influencing metabolic and energy reprogramming. This finding may offer a potential new strategy for preventing and treating DKD initiation.
Publisher OA PDF DOI
Genomic and cellular context-dependent expression of the human ELMO1 gene transcript variants
Gene · 2025-03-26 · 2 citations
articleOpen access1st author
• Human ELMO1 gene has at least five transcript variants with individual first exons. • Two of the variants are driven by endogenous retroviral LTR s, LTR12 and LTR12D . • Epigenetic influence on the ELMO1 gene expression is cell- and variant-specific. • V2 transcript encoding C-terminal 245 aa of Elmo1 protein is abundant in the brain. Engulfment and cell motility protein 1 (Elmo1) forms a complex with Dedicator of cytokinesis (Dock) 1–5 and promotes GTP-loading of Rac1, the major agent of cell movement. While the pathophysiological roles of Elmo1 have expanded from apoptotic cell engulfment to cancer, inflammation, diabetic nephropathy and cardiomyopathy, little information is available on its transcriptional regulation. Genome databases indicate at least five transcript variants for human ELMO1 : the variants V1 , V4 and V5 encode a full-length 727 aa protein, whereas V2 and V3 encode a truncated Elmo1 of 247 aa that lacks N-terminal domains. A CpG island promoter drives the major V1 transcript, while an LTR12 drives V5 in intron 1, one of the three LTR12 family of retroviral elements in ELMO1 . In contrast, the short-forms V2 and V3 contain CAT-TATA type promoters. Examination of various cell lines by RT-qPCR designed to detect individual transcripts showed that basal transcriptions of the variants were very low to undetectable in cultured cells. However, treatments with Trichostatin A, a histone deacetylase inhibitor, or with 5-Aza-2′-deoxycytidine, a DNA methyl transferase inhibitor, significantly upregulated V1 , V4 , V5 and V2 expression in a cell line-specific manner, indicating that these transcripts are epigenetically regulated. Another LTR12D transposon in intron 13 also drives an unannotated transcript stimulated by these inhibitors. Finally, we found the levels of V2 transcripts in the mouse and human brain exceed those of V1 , suggesting a brain-specific regulation and role of V2 protein.
Publisher DOI
Quantitative PPARγ expression affects the balance between tolerance and immunity
UNC Libraries · 2024-08-27
articleOpen access
Publisher DOI
Inguinal Fat Compensates Whole Body Metabolic Functionality in Partially Lipodystrophic Mice with Reduced PPARγ Expression
International Journal of Molecular Sciences · 2023-02-15 · 2 citations
articleOpen access
Peroxisome proliferator-activated receptor γ (PPARγ) gene mutations in humans and mice lead to whole-body insulin resistance and partial lipodystrophy. It is unclear whether preserved fat depots in partial lipodystrophy are beneficial for whole-body metabolic homeostasis. We analyzed the insulin response and expression of metabolic genes in the preserved fat depots of PpargC/- mice, a familial partial lipodystrophy type 3 (FPLD3) mouse model resulting from a 75% decrease in Pparg transcripts. Perigonadal fat of PpargC/- mice in the basal state showed dramatic decreases in adipose tissue mass and insulin sensitivity, whereas inguinal fat showed compensatory increases. Preservation of inguinal fat metabolic ability and flexibility was reflected by the normal expression of metabolic genes in the basal or fasting/refeeding states. The high nutrient load further increased insulin sensitivity in inguinal fat, but the expression of metabolic genes became dysregulated. Inguinal fat removal resulted in further impairment of whole-body insulin sensitivity in PpargC/- mice. Conversely, the compensatory increase in insulin sensitivity of the inguinal fat in PpargC/- mice diminished as activation of PPARγ by its agonists restored insulin sensitivity and metabolic ability of perigonadal fat. Together, we demonstrated that inguinal fat of PpargC/- mice plays a compensatory role in combating perigonadal fat abnormalities.
Publisher OA PDF DOI
TIMP3 promotes the maintenance of neural stem-progenitor cells in the mouse subventricular zone
Frontiers in Neuroscience · 2023 · 7 citations
- Biology
- Cell biology
- Neuroscience
were expressed at high levels in slowly dividing NPCs compared to rapidly dividing NPCs. Deletion of TIMP3 reduced the number of adult NSCs and neuroblasts in the lateral SVZ. In addition, overexpression of TIMP3 in the embryonic NPCs suppressed neuronal differentiation and upregulated the expression levels of Notch signaling relating genes. These results thus suggest that TIMP3 keeps the undifferentiated state of embryonic NPCs, leading to the establishment and maintenance of adult NSCs.
Publisher OA PDF DOI
Absolute Winding Number Differentiates Mouse Spatial Navigation Strategies With Genetic Risk for Alzheimer’s Disease
UNC Libraries · 2022-08-13
articleOpen accessSenior author
Spatial navigation and orientation are emerging as promising markers for altered cognition in prodromal Alzheimer’s disease, and even in cognitively normal individuals at risk for Alzheimer’s disease. The different APOE gene alleles confer various degrees of risk. The APOE2 allele is considered protective, APOE3 is seen as control, while APOE4 carriage is the major known genetic risk for Alzheimer’s disease. We have used mouse models carrying the three humanized APOE alleles and tested them in a spatial memory task in the Morris water maze. We introduce a new metric, the absolute winding number, to characterize the spatial search strategy, through the shape of the swim path. We show that this metric is robust to noise, and works for small group samples. Moreover, the absolute winding number better differentiated APOE3 carriers, through their straighter swim paths relative to both APOE2 and APOE4 genotypes. Finally, this novel metric supported increased vulnerability in APOE4 females. We hypothesized differences in spatial memory and navigation strategies are linked to differences in brain networks, and showed that different genotypes have different reliance on the hippocampal and caudate putamen circuits, pointing to a role for white matter connections. Moreover, differences were most pronounced in females. This departure from a hippocampal centric to a brain network approach may open avenues for identifying regions linked to increased risk for Alzheimer’s disease, before overt disease manifestation. Further exploration of novel biomarkers based on spatial navigation strategies may enlarge the windows of opportunity for interventions. The proposed framework will be significant in dissecting vulnerable circuits associated with cognitive changes in prodromal Alzheimer’s disease.
Publisher DOI

Recent grants

Animal Models for Studying the Genetics of Complex Diseases
NIH · $21.6M · 1992–2026
NIH Grant R01HL042630
NIH · $7.4M · 2018
NIH Grant R01HL062845
NIH · $1.0M · 2003
NIH Grant R01GM037567
NIH · $1.8M · 1999
NIH Grant R37HL042630
NIH · $4.2M · 2008

Frequent coauthors

Yau-Sheng Tsai
National Cheng Kung University Hospital
96 shared
Oliver Smithies
University of North Carolina at Chapel Hill
68 shared
E. Dale Abel
University of California, Los Angeles
64 shared
Momtaz K. Wassef
New York University
64 shared
Song‐Kun Shyue
Institute of Biomedical Sciences, Academia Sinica
64 shared
Hsin-Da Tsai
Academia Sinica
64 shared
Jin-Jer Chen
China Medical University
64 shared
Donald A. McClain
64 shared

Awards & honors

Method to Extend Research in Time (MERIT) Award from the Nat…

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