Mapping lipid species remodeling in high fat diet-fed mice: Unveiling adipose tissue dysfunction with Raman microspectroscopy

Dysregulated lipid metabolism in obesity leads to adipose tissue expansion, a major contributor to metabolic dysfunction and chronic disease. Lipid metabolism and fatty acid changes play vital roles in the progression of obesity. In this proof-of-concept study, Raman techniques combined with histochemical imaging methods were utilized to analyze the impact of a high-fat diet (HFD) on different types of adipose tissue in mice, using a small sample size (n = 3 per group). After six weeks of high-fat diet (HFD) feeding, our findings showed hypertrophy, elevated collagen levels, and increased macrophage presence in the adipose tissues of the HFD group compared to the low-fat diet (LFD) group. Statistical analysis of Raman spectra revealed significantly lower unsaturated lipid levels and higher lipid to protein content in different fat pads (brown adipose tissue (BAT), subcutaneous white adipose tissue (SWAT), and visceral white adipose tissue (VWAT)) with HFD. Raman images of adipose tissues were analyzed using Empty modeling and DCLS methods to spatially profile unsaturated and saturated lipid species in the tissues. It revealed elevated levels of ω-3, ω-6, cholesterol, and triacylglycerols in BAT adipose tissues of HFD compared to LFD tissues. These findings indicated that while cholesterol, ω-6/ω-3 ratio, and triacylglycerol levels have risen in the SWAT and VWAT adipose tissues of the HFD group, the levels of ω-3 and ω-6 have decreased following the HFD. The study showed that Raman spectroscopy provided invaluable information at the molecular level for investigating lipid species remodeling and spatial mapping of adipose tissues during HFD.