PMID- 37175908
OWN - NLM
STAT- MEDLINE
DCOM- 20230515
LR  - 20230515
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 9
DP  - 2023 May 3
TI  - Unraveling the Host Genetic Background Effect on Internal Organ Weight Influenced 
      by Obesity and Diabetes Using Collaborative Cross Mice.
LID - 10.3390/ijms24098201 [doi]
LID - 8201
AB  - Type 2 diabetes mellitus (T2DM) is a severe chronic epidemic that results from 
      the body's improper usage of the hormone insulin. Globally, 700 million people 
      are expected to have received a diabetes diagnosis by 2045, according to the 
      International Diabetes Federation (IDF). Cancer and macro- and microvascular 
      illnesses are only a few immediate and long-term issues it could lead to. T2DM 
      accelerates the effect of organ weights by triggering a hyperinflammatory 
      response in the body's organs, inhibiting tissue repair and resolving 
      inflammation. Understanding how genetic variation translates into different 
      clinical presentations may highlight the mechanisms through which dietary 
      elements may initiate or accelerate inflammatory disease processes and suggest 
      potential disease-prevention techniques. To address the host genetic background 
      effect on the organ weight by utilizing the newly developed mouse model, the 
      Collaborative Cross mice (CC). The study was conducted on 207 genetically 
      different CC mice from 8 CC lines of both sexes. The experiment started with 
      8-week-old mice for 12 weeks. During this period, one group maintained a standard 
      chow diet (CHD), while the other group maintained a high-fat diet (HFD). In 
      addition, body weight was recorded bi-weekly, and at the end of the study, a 
      glucose tolerance test, as well as tissue collection (liver, spleen, heart), were 
      conducted. Our study observed a strong effect of HFD on blood glucose clearance 
      among different CC lines. The HFD decreased the blood glucose clearance displayed 
      by the significant Area Under Curve (AUC) values in both populations. In 
      addition, variation in body weight changes among the different CC lines in 
      response to HFD. The female liver weight significantly increased compared to 
      males in the overall population when exposed to HFD. Moreover, males showed 
      higher heritability values than females on the same diet. Regardless of the 
      dietary challenge, the liver weight in the overall male population correlated 
      positively with the final body weight. The liver weight results revealed that 
      three different CC lines perform well under classification models. The regression 
      results also varied among organs. Accordingly, the differences among these lines 
      correspond to the genetic variance, and we suspect that some genetic factors 
      invoke different body responses to HFD. Further investigations, such as 
      quantitative trait loci (QTL) analysis and genomic studies, could find these 
      genetic elements. These findings would prove critical factors for developing 
      personalized medicine, as they could indicate future body responses to numerous 
      situations early, thus preventing the development of complex diseases.
FAU - Ghnaim, Aya
AU  - Ghnaim A
AD  - Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, 
      Tel-Aviv University, Tel-Aviv 69978, Israel.
FAU - Lone, Iqbal M
AU  - Lone IM
AD  - Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, 
      Tel-Aviv University, Tel-Aviv 69978, Israel.
FAU - Nun, Nadav Ben
AU  - Nun NB
AD  - Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, 
      Tel-Aviv University, Tel-Aviv 69978, Israel.
FAU - Iraqi, Fuad A
AU  - Iraqi FA
AUID- ORCID: 0000-0001-5525-206X
AD  - Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, 
      Tel-Aviv University, Tel-Aviv 69978, Israel.
LA  - eng
GR  - 2015077/United States-Israel Binational Science Foundation/
GR  - 1085/18/Israel Science Foundataion/
GR  - I-63-410.20-2017/German Israel Science Foundation/
GR  - 111/Tel-Aviv Core Fund/
PT  - Journal Article
DEP - 20230503
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Blood Glucose)
SB  - IM
MH  - Male
MH  - Female
MH  - Mice
MH  - Animals
MH  - *Blood Glucose
MH  - *Diabetes Mellitus, Type 2/genetics
MH  - Collaborative Cross Mice
MH  - Organ Size
MH  - Obesity/genetics
MH  - Diet, High-Fat/adverse effects
PMC - PMC10179483
OTO - NOTNLM
OT  - Collaborative Cross mice
OT  - genetic effect
OT  - heritability
OT  - high fat diet effect on organs' weight
OT  - machine learning
OT  - obesity
OT  - type 2 diabetes mellitus (T2DM)
COIS- On behalf of all authors, the corresponding author states that there are no 
      conflicts of interest.
EDAT- 2023/05/13 15:13
MHDA- 2023/05/15 11:42
PMCR- 2023/05/03
CRDT- 2023/05/13 01:29
PHST- 2023/02/25 00:00 [received]
PHST- 2023/04/09 00:00 [revised]
PHST- 2023/04/28 00:00 [accepted]
PHST- 2023/05/15 11:42 [medline]
PHST- 2023/05/13 15:13 [pubmed]
PHST- 2023/05/13 01:29 [entrez]
PHST- 2023/05/03 00:00 [pmc-release]
AID - ijms24098201 [pii]
AID - ijms-24-08201 [pii]
AID - 10.3390/ijms24098201 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 May 3;24(9):8201. doi: 10.3390/ijms24098201.