PMID- 35842612
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220719
IS  - 1555-8932 (Print)
IS  - 1865-3499 (Electronic)
IS  - 1555-8932 (Linking)
VI  - 17
IP  - 1
DP  - 2022 Jul 16
TI  - Vitamin C attenuates predisposition to high-fat diet-induced metabolic 
      dysregulation in GLUT10-deficient mouse model.
PG  - 10
LID - 10.1186/s12263-022-00713-y [doi]
LID - 10
AB  - BACKGROUND: The development of type 2 diabetes mellitus (T2DM) is highly 
      influenced by complex interactions between genetic and environmental (dietary and 
      lifestyle) factors. While vitamin C (ascorbic acid, AA) has been suggested as a 
      complementary nutritional treatment for T2DM, evidence for the significance and 
      beneficial effects of AA in T2DM is thus far inconclusive. We suspect that 
      clinical studies on the topic might need to account for combination of genetic 
      and dietary factors that could influence AA effects on metabolism. In this study, 
      we tested this general idea using a mouse model with genetic predisposition to 
      diet-induced metabolic dysfunction. In particular, we utilized mice carrying a 
      human orthologous GLUT10(G128E) variant (GLUT10(G128E) mice), which are highly 
      sensitive to high-fat diet (HFD)-induced metabolic dysregulation. The genetic 
      variant has high relevance to human populations, as genetic polymorphisms in 
      glucose transporter 10 (GLUT10) are associated with a T2DM intermediate phenotype 
      in nondiabetic population. RESULTS: We investigated the impacts of AA 
      supplementation on metabolism in wild-type (WT) mice and GLUT10(G128E) mice fed 
      with a normal diet or HFD. Overall, the beneficial effects of AA on metabolism 
      were greater in HFD-fed GLUT10(G128E) mice than in HFD-fed WT mice. At early 
      postnatal stages, AA improved the development of compromised epididymal white 
      adipose tissue (eWAT) in GLUT10(G128E) mice. In adult animals, AA supplementation 
      attenuated the predisposition of GLUT10(G128E) mice to HFD-triggered eWAT 
      inflammation, adipokine dysregulation, ectopic fatty acid accumulation, metabolic 
      dysregulation, and body weight gain, as compared with WT mice. CONCLUSIONS: Taken 
      together, our findings suggest that AA has greater beneficial effects on 
      metabolism in HFD-fed GLUT10(G128E) mice than HFD-fed WT mice. As such, AA plays 
      an important role in supporting eWAT development and attenuating HFD-induced 
      metabolic dysregulation in GLUT10(G128E) mice. Our results suggest that proper 
      WAT development is essential for metabolic regulation later in life. Furthermore, 
      when considering the usage of AA as a complementary nutrition for prevention and 
      treatment of T2DM, individual differences in genetics and dietary patterns should 
      be taken into account.
CI  - (c) 2022. The Author(s).
FAU - Jiang, Chung-Lin
AU  - Jiang CL
AD  - Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
FAU - Tsao, Chang-Yu
AU  - Tsao CY
AD  - Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
FAU - Lee, Yi-Ching
AU  - Lee YC
AUID- ORCID: 0000-0002-7734-5619
AD  - Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan. 
      yiching@gate.sinica.edu.tw.
LA  - eng
GR  - MOST107-2320-B-001-024 and MOST 108-2320-B-001-022/Ministry of Science and 
      Technology (MOST), Taiwan/
GR  - AS 105-TP-B04/Academia Sinica, Taiwan/
PT  - Journal Article
DEP - 20220716
PL  - Germany
TA  - Genes Nutr
JT  - Genes & nutrition
JID - 101280108
PMC - PMC9288715
OTO - NOTNLM
OT  - Genetic predisposition
OT  - High-fat diet
OT  - Type 2 diabetes mellitus
OT  - Vitamin C
OT  - White adipose tissue
COIS- The authors declare that they have no competing interests.
EDAT- 2022/07/17 06:00
MHDA- 2022/07/17 06:01
PMCR- 2022/07/16
CRDT- 2022/07/16 23:26
PHST- 2022/03/07 00:00 [received]
PHST- 2022/06/21 00:00 [accepted]
PHST- 2022/07/16 23:26 [entrez]
PHST- 2022/07/17 06:00 [pubmed]
PHST- 2022/07/17 06:01 [medline]
PHST- 2022/07/16 00:00 [pmc-release]
AID - 10.1186/s12263-022-00713-y [pii]
AID - 713 [pii]
AID - 10.1186/s12263-022-00713-y [doi]
PST - epublish
SO  - Genes Nutr. 2022 Jul 16;17(1):10. doi: 10.1186/s12263-022-00713-y.