Deep Multi-OMICs and Multi-Tissue Characterization in a Pre- and Postprandial State in Human Volunteers: The GEMM Family Study Research Design

Abstract

Cardiovascular disease (CVD) and type 2 diabetes (T2D) are increasing worldwide. This is mainly due to an unhealthy nutrition, implying that variation in CVD risk may be due to variation in the capacity to manage a nutritional load. We examined the genomic basis of postprandial metabolism. Our main purpose was to introduce the GEMM Family Study (Genetics of Metabolic Diseases in Mexico) as a multi-center study carrying out an ongoing recruitment of healthy urban adults. Each participant received a mixed meal challenge and provided a 5-hours’ time course series of blood, buffy coat specimens for DNA isolation, and adipose tissue (ADT)/skeletal muscle (SKM) biopsies at fasting and 3 h after the meal. A comprehensive profiling, including metabolomic signatures in blood and transcriptomic and proteomic profiling in SKM and ADT, was performed to describe tendencies for variation in postprandial response. Our data generation methods showed preliminary trends indicating that by characterizing the dynamic properties of biomarkers with metabolic activity and analyzing multi-OMICS data it could be possible, with this methodology and research design, to identify early trends for molecular biology systems and genes involved in the fasted and fed states.

Replication of Integrative Data Analysis for Adipose Tissue Dysfunction, Low-Grade Inflammation, Postprandial Responses and OMICs Signatures in Symptom-Free Adults

“…Recruitment of study participants: As of February 2020, GEMM had performed the meal challenge, tissue biopsies and sample collection for 225 participants [ 14 , 15 ]. Unfortunately, the COVID-19 pandemic forced us to temporarily stop recruitment.…”

“…However, we were able to bring samples from 124 study participants to the US in December 2019 and have obtained data from these recruited participants (81 females and 43 males). Our cohort is comprised of SF volunteers that were carefully screened to rule out presence of any chronic or acute inflammatory disease, as described in detail elsewhere [ 14 , 15 , 16 ].…”

“…Plasma samples were transported to Dr. Xianlin Han’s laboratory at the University of Texas Health Sciences Center San Antonio [ 21 ]. Lipids were extracted with chloroform/methanol in the presence of a cocktail of internal standards [ 22 ] and analyzed by multi-dimensional mass spectrometry-based shotgun lipidomics (MDMS-SL), as previously described [ 14 , 15 , 23 ].…”

“…Our measurements in blood and tissues were taken over a time course to allow fine scale multi-OMIC profiling of individual postprandial responses. Unlike studies utilizing tissue repositories of poorly-characterized origin, our study obtained tissues from a well-characterized cohort of symptom-free adults of common ancestry [ 14 , 15 ].…”

The COVID-19 Pandemic during the Time of the Diabetes Pandemic: Likely Fraternal Twins?

“…They are the leading cause of death across the world. These pathologies are associated with multiple immune risk factors of metabolic origin that may not be obvious in symptom-free individuals [49,50]. Recent research has increased our awareness of the key role that adipose tissue (AT) dysfunction plays in the development of IR, the underlying cause of T2D and other immunometabolic diseases [51].…”