An Integrated Multi-Omics Analysis Defines Key Pathway Alterations in a Diet-Induced Obesity Mouse Model.

Obesity is a multifactorial disease with many complications and related diseases and has become a global epidemic. To thoroughly understand the impact of obesity on whole organism homeostasis, it is helpful to utilize a systems biological approach combining gene expression and metabolomics across tissues and biofluids together with metagenomics of gut microbial diversity. Here, we present a multi-omics study on liver, muscle, adipose tissue, urine, plasma, and feces on mice fed a high-fat diet (HFD). Gene expression analyses showed alterations in genes related to lipid and energy metabolism and inflammation in liver and adipose tissue. The integration of metabolomics data across tissues and biofluids identified major differences in liver TCA cycle, where malate, succinate and oxaloacetate were found to be increased in HFD mice. This finding was supported by gene expression analysis of TCA-related enzymes in liver, where expression of malate dehydrogenase was found to be decreased. Investigations of the microbiome showed enrichment of Lachnospiraceae, Ruminococcaceae, Streptococcaceae and Lactobacillaceae in the HFD group. Our findings help elucidate how the whole organism metabolome and transcriptome are integrated and regulated during obesity.

Lack of sex differences in modulation of experimental intraoral pain by diffuse noxious inhibitory controls (DNIC).

The aims of this study were to investigate possible sex differences in (a) intraoral pain evoked by topical application of capsaicin to the gingiva, and (b) the modulation of this pain by diffuse noxious inhibitory controls (DNIC). Three groups with a total of fifty-four healthy volunteers (20 men, 20 women using oral contraceptives (W+OC), 14 women not using (W-OC)) completed the study. In two sessions, intraoral pain was evoked by topical application of 30microL 5% capsaicin to the gingiva. Conditioning stimuli were applied with three min hand immersion in ice water in one session and 30 degrees C water (control) in another session. The capsaicin-evoked pain and the water-evoked pain were evaluated by the participants on visual analogue scales (VAS). No main effects of group in capsaicin-evoked pain (P>0.062) or water-evoked pain (P>0.149) were found. There was a significant group x time interaction (P<0.001) with W+OC reporting lower capsaicin-evoked pain scores than W-OC in the early phase (2-3min) and lower pain scores than men in the later phase (5-11min). The degree of modulation by DNIC did not differ between groups (P=0.636). In conclusion, for a superficial type of intraoral pain, only minor sex differences were found in pain intensity and no differences in the degree of endogenous modulation by DNIC. Female sex and the use of OC may not consistently be associated with higher sensitivity to pain.