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

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.