Transcriptomics analysis of differentially expressed genes in subcutaneous and perirenal adipose tissue of sheep as affected by their pre- and early postnatal malnutrition histories

Abstract

Background Early life malnutrition is known to target adipose tissue with varying impact depending on timing of the insult. This study aimed to identify differentially expressed genes in subcutaneous (SUB) and perirenal (PER) adipose tissue of 2.5-years old sheep to elucidate the biology underlying differential impacts of late gestation versus early postnatal malnutrition on functional development of adipose tissues. Adipose tissues were obtained from 37 adult sheep born as twins to dams fed either NORM (fulfilling energy and protein requirements), LOW (50% of NORM) or HIGH (110% of protein and 150% of energy requirements) diets in the last 6-weeks of gestation. From day 3 to 6 months of age, lambs were fed high-carbohydrate-high-fat (HCHF) or moderate low-fat (CONV) diets, and thereafter the same moderate low-fat diet. Results The gene expression profile of SUB in the adult sheep was not affected by the pre- or early postnatal nutrition history. In PER, 993 and 186 differentially expressed genes (DEGs) were identified in LOW versus HIGH and NORM, respectively, but no DEG was found between HIGH and NORM. DEGs identified in the mismatched pre- and postnatal nutrition groups LOW-HCHF (101) and HIGH-HCHF (192) were largely downregulated compared to NORM-CONV. Out of 831 DEGs, 595 and 236 were up- and downregulated in HCHF versus CONV, respectively. The functional enrichment analyses revealed that transmembrane (ion) transport activities, motor activities related to cytoskeletal and spermatozoa function (microtubules and the cytoskeletal motor protein, dynein), and responsiveness to the (micro) environmental extracellular conditions, including endocrine and nervous stimuli were enriched in the DEGs of LOW versus HIGH and NORM. We confirmed that mismatched pre- and postnatal feeding was associated with long-term programming of adipose tissue remodeling and immunity-related pathways. In agreement with phenotypic measurements, early postnatal HCHF feeding targeted pathways involved in kidney cell differentiation, and mismatched LOW-HCHF sheep had specific impairments in cholesterol metabolism pathways. Conclusions Both pre- and postnatal malnutrition differentially programmed (patho-) physiological pathways with implications for adipose functional development associated with metabolic dysfunctions, and PER was a major target.

The Impact of SLC2A8 RNA Interference on Glucose Uptake and the Transcriptome of Human Trophoblast Cells

“…Research on energy restriction during late gestation and the muscle and blood transcriptome of beef calves revealed that impaired glucose metabolism may affect genes involved in cellular respiration, including ETFRF1 [ 58 ]. ETFRF1 was also listed among the genes that were dysregulated in subcutaneous and perirenal adipose tissue of sheep as a resultant of pre- and early postnatal malnutrition [ 59 ]. In the current research, ETFRF1 expression was downregulated as a consequence of the diminished SLC2A8 expression.…”

Full-Length Transcriptome and Gene Expression Analysis of Different Ovis aries Adipose Tissues Reveals Transcript Variants Involved in Lipid Biosynthesis

“…Numerous molecular mechanisms associated with fat metabolism in sheep have been investigated [ 3 , 11 , 35 ]. However, the genetic mechanism at the transcriptional level of fat metabolism remains unclear.…”

“…Gene transcripts undergo diverse splicing to generate various isoforms. With the commercialization of sequencing platforms and the reduced sequencing costs, transcriptome sequencing technology has found widespread application in animal transcriptome studies, including pigs [ 7 ], chickens [ 8 ], beef cattle [ 9 ], goats [ 10 ], and sheep [ 11 ]. Previous studies on sheep fat metabolism have primarily focused on short-read RNA-seq data from second-generation sequencing platforms [ 11 , 12 , 13 ].…”

“…With the commercialization of sequencing platforms and the reduced sequencing costs, transcriptome sequencing technology has found widespread application in animal transcriptome studies, including pigs [ 7 ], chickens [ 8 ], beef cattle [ 9 ], goats [ 10 ], and sheep [ 11 ]. Previous studies on sheep fat metabolism have primarily focused on short-read RNA-seq data from second-generation sequencing platforms [ 11 , 12 , 13 ]. The primary objectives of these studies were to describe gene expression levels and explore the differentially expressed genes related to lipid metabolism.…”

Gene coexpression network analysis reveals perirenal adipose tissue as an important target of prenatal malnutrition in sheep

“…Large animal models such as sheep have previously been used to investigate the interplay between insulin sensitivity, type II diabetes, and metabolic response to exercise and adiposity ( 7 – 9 ). Similarly, using the Copenhagen sheep model, we have previously demonstrated significant changes in the PER transcriptome of 2.5-yr-old adults exposed to prenatal undernutrition (LOW) followed by a mismatching obesogenic, high-carbohydrate-high-fat (HCHF) diet during the first 6 mo of life (adolescent lambs) ( 10 ). In these nutritionally mismatched LOW-HCHF adult sheep, the affected molecular pathways included cholesterol metabolism, whereas early postnatal HCHF feeding targeted biological processes related to kidney cell differentiation.…”