Synchrotron infrared imaging of advanced glycation endproducts (AGEs) in cardiac tissue from mice fed high glycemic diets

Abstract

Recent research findings correlate an increased risk for dieases such as diabetes, macular degeneration and cardiovascular disease (CVD) with diets that rapidly raise the blood sugar levels; these diets are known as high glycemic index (GI) diets which include white breads, sodas and sweet deserts. Lower glycemia diets are usually rich in fruits, non-starchy vegetables and whole grain products. The goal of our study was to compare and contrast the effects of a low vs. high glycemic diet using 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 allowed not only fine-scale chemical analyses of glycogen and glycolipid accumulation along a vein as well as protein glycation hotspots co-localizing with collagen cold spots but also the 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. Our results bring a new insight 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.

Metabolic Effects of High Glycaemic Index Diets: A Systematic Review and Meta-Analysis of Feeding Studies in Mice and Rats

“…The systematic search procedure with the number of articles included and excluded at each point is depicted in Figure 1 . The end result was 30 articles, with 15 [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ] involving mice, 13 [ 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ] involving rats and two [ 56 , 57 ] with experiments performed on both species. Of the articles that contained pertinent results, all contained information regarding the change or comparison of body weight or fat, and most examined some measure of glucose homeostasis.…”

“…Unfortunately, many articles lacked specific details relating to diet composition. We included six articles where the macronutrient content was stated, but not explicated to whether this percentage was of weight or energy [ 29 , 30 , 31 , 35 , 38 , 40 ]. Criteria for this review required carbohydrate contribution to energy greater than 50%, and, as protein, fat and carbohydrates have different energy densities, if the given content was of weight, some articles may not have actually met these criteria; accordingly, these articles were excluded.…”

“…The animal age at commencement of study and the length of study varied considerably. Most of the mice studies [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 56 , 57 ] utilized adult animals, ranging in age from 8 weeks to 16 months at the start of the study, while several rat studies used animals that were 6 weeks old or younger [ 43 , 44 , 45 , 47 , 48 , 49 , 55 , 56 ]. Two rat studies did not provide the starting age of animals, thus their developmental state is unknown [ 46 , 54 ].…”

“…One of these studies [ 54 ] is a study of the maternal effect of diet, so it could be assumed that the rats were mature, but the other [ 46 ] gave no age indication, and only lasted for two weeks, thus these rats may not be fully developed even at the completion of the study. Most of the mice studies were relatively long studies, consisting of interventions lasting at least 16 weeks [ 29 , 31 , 32 , 34 , 35 , 36 , 38 , 39 , 40 , 41 , 42 ] compared to the majority of rat studies lasting only 4–8 weeks, with only four lasting longer than eight weeks [ 43 , 44 , 54 , 56 ]. Due to the young age and short length of study, it is possible that the animals in some of these experiments [ 30 , 43 , 45 , 46 , 47 , 48 , 49 , 52 , 53 , 55 , 56 ] are still in an adolescence period and hence the results may not reflect the generalized effects of HGI or LGI diets.…”

“…The MQA question on power relied on sample size, hence the eight studies that did not provide sample size [ 38 , 40 , 42 , 43 , 46 , 47 , 48 , 49 , 57 ] received a potentially lower MQA score for this lack of information. Of all 30 articles, only eight had sufficient power [ 30 , 31 , 33 , 37 , 44 , 45 , 54 , 55 ] with a sample size of 14 or greater per group.…”