Gene-by-diet interactions influence calcium absorption and bone density in mice

Area of Science:

• Nutritional science
• Genetics
• Bone metabolism

Background:

• Dietary calcium (Ca) is crucial for peak bone mineral density (BMD).
• Low Ca intake enhances intestinal Ca absorption efficiency to preserve bone mass.
• The mechanisms and genetic influences on this adaptive response are not fully understood.

Purpose of the Study:

• To investigate the independent and interacting effects of diet and genetics on Ca and bone metabolism.
• To identify genetic variations influencing Ca absorption and bone adaptation to low Ca diets.
• To explore the relationship between Ca absorption, bone parameters, and specific intestinal proteins.

Main Methods:

• Fed 11 genetically diverse mouse lines normal (0.5%) or low (0.25%) Ca diets from 4 to 12 weeks of age.
• Measured bone, renal, and intestinal phenotypes, including Ca absorption and 1,25 dihydroxyvitamin D (1,25(OH)2 D) levels.
• Analyzed mRNA levels of key intestinal Ca absorption proteins: TRPV6, CaBPD9k, and PMCA1b.

Main Results:

• Significant genetic variation was found in all measured phenotypes, including Ca absorption.
• Adaptation of Ca absorption and bone parameters to low Ca diets differed significantly among mouse lines.
• Ca absorption correlated positively with femur BMD and bone volume, and with 1,25(OH)2 D, but adaptation patterns did not align.
• mRNA levels of TRPV6, CaBPD9k, and PMCA1b were related to Ca absorption, but explained only a portion of the variation.

Conclusions:

• Genetics plays a substantial role in Ca absorption and bone metabolism adaptation to dietary Ca.
• Existing models do not fully explain the variation in Ca absorption, suggesting novel mechanisms.
• This study provides a foundation for identifying new genetic factors controlling gene-by-diet interactions in Ca/bone metabolism.