Obesity-Related Metabolome and Gut Microbiota Profiles of Juvenile Göttingen Minipigs—Long-Term Intake of Fructose and Resistant Starch

Abstract

The metabolome and gut microbiota were investigated in a juvenile Göttingen minipig model. This study aimed to explore the metabolic effects of two carbohydrate sources with different degrees of risk in obesity development when associated with a high fat intake. A high-risk (HR) high-fat diet containing 20% fructose was compared to a control lower-risk (LR) high-fat diet where a similar amount of carbohydrate was provided as a mix of digestible and resistant starch from high amylose maize. Both diets were fed ad libitum. Non-targeted metabolomics was used to explore plasma, urine, and feces samples over five months. Plasma and fecal short-chain fatty acids were targeted and quantified. Fecal microbiota was analyzed using genomic sequencing. Data analysis was performed using sparse multi-block partial least squares regression. The LR diet increased concentrations of fecal and plasma total short-chain fatty acids, primarily acetate, and there was a higher relative abundance of microbiota associated with acetate production such as Bacteroidetes and Ruminococcus. A higher proportion of Firmicutes was measured with the HR diet, together with a lower alpha diversity compared to the LR diet. Irrespective of diet, the ad libitum exposure to the high-energy diets was accompanied by well-known biomarkers associated with obesity and diabetes, particularly branched-chain amino acids, keto acids, and other catabolism metabolites.

Obesity Development and Signs of Metabolic Abnormalities in Young Göttingen Minipigs Consuming Energy Dense Diets Varying in Carbohydrate Quality

“…We were expecting that the higher fermentation of RS in the LR diet would have a direct effect on satiety control mechanisms [ 25 ] and thereby influence the ad libitum feed intake. Previously published data on gut microbiota revealed a higher abundance of microbiota associated with acetate production ( Bacteroidetes and Ruminococcus ) and fecal and plasma SCFA in the LR diet [ 19 ]. This, together with the higher release of PYY throughout the trial, is in agreement with previous studies in swine [ 24 ], but in contrast to our expectations where the feed intake of the LR group was higher than of the HR group.…”

“…This, together with the higher release of PYY throughout the trial, is in agreement with previous studies in swine [ 24 ], but in contrast to our expectations where the feed intake of the LR group was higher than of the HR group. A reason for that could be the higher acetate production in the LR group [ 19 ] causing acetate-mediated hyperphagia in an ad libitum context, as recently found in a rodent study [ 32 ]. Other studies applying ad libitum feeding with RS to pigs have also failed to influence voluntary feed intake and carcass quality compared to a low-RS diet [ 33 , 34 ].…”

“…Irrespective of the carbohydrate quality of the diets, there was a down-regulation of GLUT4 expression in muscle and SAT, towards the end of the dietary intervention, which indicates an early progression toward insulin resistance and T2D pathogenesis as has been found in adipose tissue GLUT4 knockdown mice that developed insulin resistance [ 41 ], whereas overexpression of GLUT4 in adipocytes reduced fasting hyperglycemia and prevented insulin resistance [ 42 ]. Branched-chain amino acids (BCAA, leucine, valine) are linked to insulin resistance via GLUT4 [ 43 ] and the accumulation of BCAA and BCAA degradation products found in our metabolomic study [ 19 ] could be an early sign of insulin resistance as further indicated by the significantly increased plasma levels of glucose ( p = 0.005), fructosamine ( p < 0.001), insulin ( p = 0.03), and HOMA-IR ( p = 0.02) in both groups from week 4 to week 20. In spite of these changes in metabolic biomarkers, the minipigs developed only some of the hallmarks of MetS; increased body weight, BSA, and POI with visible deposition of subcutaneous fat, alterations in fasting glucose, and insulin responses, and decreasing levels of HDL cholesterol.…”

“…It is hypothesized that fructose, because of its metabolic effects, will lead to a more rapid development of obesity and markers of metabolic abnormalities of the young Göttingen Minipigs. This paper is a continuation on the study of Curtasu et al (2020), where samples collected from this miniature pig model were previously assessed from a metabolomics and gut microbiota profiling perspective [19].…”

Assessment of Biotechnologically Important Filamentous Fungal Biomass by Fourier Transform Raman Spectroscopy

“…Consensus principal component analysis (CPCA) was used on multiblock spectral data, consisting of preprocessed derivative FTIR and FT-Raman data blocks. In CPCA, technical replicates were averaged after the preprocessing in order to obtain sample-to-sample correspondence between the data blocks [77,86,87].…”