Identifying diet-induced advanced glycation endproducts

The Taylor Group at Tufts University focuses on improving current understandings on diet-induced advanced glycation endproducts (AGEs). The growing obesity, and diabetes epidemics make it imperative to develop new means to diagnose and treat these and associated diseases including macular degeneration and cardiovascular disease (CVD).

A considerable literature indicates the dangers of high glycemic index (GI) diets that are high in rapidly digested starches, with respect to risk for these diseases.

Comparative analysis of SR-FTIR and auto-fluorescence images shows different types of advanced glycation endproducts (AGEs) hotspots in cardiac tissue sections from high GI-fed mice. (A) The spatial distribution of the values of the ratio of carbohydrate band to protein ratio (in a logarithmic scale from -3 to 0.0) (B) the fluorescence images (excitation 450-490 nm, emission 500-550 nm) of the same region. White squares mark areas of fluorescence AGE hotspots (as elevated values of the ratio of carbohydrate to proteins and as bright spots in the fluorescence images), red squares mark areas of non-fluorescence AGE hotspots. Insets: heatmaps of Integrated absorbance of sugar moieties of carbohydrates (in linear scale from 0 to 12 a.u.). Below the heatmap insets are the corresponding SR-FTIR spectra of each “hotspot” in red (fingerprint region and lipid region) compared to the average spectrum of the HGI tissue (in black).

The goal of the study was to compare and contrast the effects of a low vs. high glycemic diet on the biochemical composition and microstructure of the heart. The improved spatial resolution and signal-to-noise for SR-FTIR obtained through the coupling of the bright synchrotron infrared photon source to an infrared spectral microscope enabled the molecular-level observation of diet-related changes within unfixed fresh frozen histologic sections of mouse cardiac tissue.

High and low glycemic index (GI) diets were started at the age of five-months and continued for one year, with the diets only differing in their starch distribution (high GI diet = 100% amylopectin versus low GI diet = 30% amylopectin/70% amylose). Serial cryosections of cardiac tissue for SR-FTIR imaging alternated with adjacent hematoxylin and eosin (H&E) stained sections.

They allowed fine-scale chemical analyses of glycogen and glycolipid accumulation along a vein, protein glycation hotspots co-localizing with collagen cold spots, as well as tracking of morphological differences occurring in tandem with these chemical changes.

As a result of the bright synchrotron infrared photon source coupling, we were able to provide significant molecular evidence for a positive correlation between protein glycation and collagen degradation in our mouse model. 

The combined SR-FTIR spectromicroscopy and fluorescence imaging results bring new insights not only to the effects of long-term GI dietary practices of the public but also to the molecular and chemical foundation behind the cardiovascular disease pathogenesis commonly seen in diabetic patients.