Background: It’s known that laboratory mouse strains respond differently to high caloric feeding in terms of their adiposity and glucose tolerance. However, significant inter-individual variability also occurs within strains. What drives this difference given background genetics is controlled is unknown, but may reveal insights regarding maintenance of leanness.
Methods: We screened 30 C57BL6/J mice fed a high fat/high sucrose diet (HFHS) for 8-weeks and identified three mice discordant for adiposity (i.e. they remained lean) compared to their littermate cage-mates. Lipidomic and proteomic analysis was then conducted on metabolic tissues.
Results: After 8 weeks of the HFHS diet, the lean mice had an average of 6.69gms less adipose tissue than their matched controls (p = <0.001) with a body fat percentage of 17.63% compared to 31.32% (p = <0.01). Lipidomic analysis identified that the lean mice had a decrease in multiple lysophosphatidylcholine (LPC) and an increase in ceramide (CER) sphingomyelin (SM) and triacylglycerol (TG) species in the adipose. LPC and SM species were elevated in the muscle of the lean mice. In the liver, diacylglycerols (DG) and TG species were decreased, while SM species were elevated in the lean group. Plasma analysis indicated a decrease in cholesterol esters (CE) and SM species. Proteomic analysis in the muscle and adipose revealed no differences between groups after catering for multiple hypotheses. In the liver Gene Ontology enrichment analysis indicated an overrepresentation of genes/proteins associated with fatty acid transport and metabolic processes in the lean animals.
Conclusion: Despite the same genetics and environment, discordance for adiposity in HFHS-fed mice is associated with specific changes in the tissue lipidomic signature. Further studies into the potential processes behind these alterations such as epigenetic or post-translational modifications are warranted.