Post-weaning high-fat diet accelerates kidney injury, but not hypertension programmed by maternal diabetes

Abstract

Background:The aim of this study was to establish the underlying mechanisms by which a post-weaning high-fat diet (HFD) accelerates the perinatal programming of kidney injury occurring in the offspring of diabetic mothers. Methods: Male mice, offspring of nondiabetic and diabetic dams were fed with normal diet (ND) or HFD from 4 to 20 wk of age. Rat renal proximal tubular cells were used in vitro. results: On ND, the offspring of dams with severe maternal diabetes had an intrauterine growth restriction (IUGR) phenotype and developed mild hypertension and evidence of kidney injury in adulthood. Exposing the IUGR offspring to HFD resulted in rapid weight gain, catch-up growth, and later to profound kidney injury with activation of renal TGFβ1 and collagen type IV expression, increased oxidative stress, and enhanced renal lipid deposition, but not systemic hypertension. Given our data, we speculate that HFD or free fatty acids may accelerate the process of perinatal programming of kidney injury, via increased CD36 and fatty acid-binding protein 4 expression, which may target reactive oxygen species, nuclear factor-kappa B, and TGFβ1 signaling in vivo and in vitro. conclusion: Early postnatal exposure to overnutrition with a HFD increases the risk of development of kidney injury, but not hypertension, in IUGR offspring of dams with maternal diabetes.d iabetes during pregnancy, whether gestational or pregestational diabetes (type 1 or type 2), results in offspring at high risk of developing hypertension, cardiovascular disease, and chronic kidney disease in adult life. This phenomenon, termed perinatal programming, in which intrauterine events are associated with later adverse changes, has attracted much attention (1-3). Substantial epidemiologic data have also suggested that the offspring whose mothers were diabetic during pregnancy are susceptible to metabolic disturbances induced by postnatal overnutrition, as seen with high-fat diet (HFD) or with increased caloric intake in early life (1)(2)(3)(4).Women who have diabetes during pregnancy and/or are obese and hyperinsulinemic are at risk of delivering macrosomic newborns (high birth weight), and both shortand long-term outcomes of macrosomic neonates are influenced by postnatal overnutrition (1-4). In high-birth-weight neonates, subsequent growth in infancy and risk of becoming obese or diabetic are directly and linearly linked-e.g., the higher the birth weight, the greater the risk of overweight and metabolic disturbances later in life (1-4). In contrast, pregnant women with severe, uncontrolled diabetes or diabetic complications, such as diabetic nephropathy and/or retinopathy, are at high risk of having a microsomic fetus (i.e., a fetus with intrauterine growth restriction (IUGR)) (5,6). Such infants may be markedly small for dates; but many develop excessive weight gain and increased fat deposition in early infancy, a proxy for neonatal overnutrition (7,8). However, the long-term outcome of IUGR offspring who experience overnutrition in early life is incomplet...

High Fat Diets Sex-Specifically Affect the Renal Transcriptome and Program Obesity, Kidney Injury, and Hypertension in the Offspring

“…Consistent with previous reports [30,31], male offspring exposed to post-weaning HF showed glomerulosclerosis, segmental necrosis, thickening in the basal membrane of glomeruli and tubules, dilatation in glomerular capillaries, and tubular dilatation (Figure 3A). Maternal and post-weaning HF were associated with greater degrees of glomerular (Figure 3B, P pre = 0.03 and P post = 0.007) and tubulointerstitial injury (Figure 3C, P pre = 0.005 and P post = 0.005) in male offspring kidneys than those in females.…”

“…Consistent with previous reports showing fibrotic and epithelial-to-mesenchymal transition (EMT) markers were augmented by HF intake [30,31,37], we found that maternal and post-weaning HF increased mRNA expression of collagen I and α-SMA in the offspring kidneys of both sexes. Noteworthy, male offspring exposed to maternal plus post-weaning HF showed greater degrees of glomerular and tubulointerstitial injury and worse renal function compared to females.…”

“…Whether sex hormones influence the vulnerability to protect female offspring against HF-induced programmed kidney disease deserves further clarification. Our findings in conjunction with others indicate that male offspring tend to be more vulnerable to HF-induced renal injury than females [30,31]. …”

Gold-quercetin nanoparticles prevent metabolic endotoxemia-induced kidney injury by regulating TLR4/NF-kB signaling and Nrf2 pathway in high fat diet fed mice

“…[1][2][3] Lately, high-fat diet (HFD)-induced inflammatory responses in the peripheral tissues, especially in liver, cardiac muscle, and kidney, have been well characterized. [4][5][6] In a previous research, HFD was found to be capable of causing 3 CKD, a progressive loss in renal function over a period of months or years, has been regarded as a threat to people all over the world. 7,8 As the final manifestation of CKD, renal fibrosis is a common pathway toward kidney failure.…”

Peer Review #2 of "CD36 identified by weighted gene co-expression network analysis as a hub candidate gene in lupus nephritis (v0.2)"

“…Meanwhile, oxidant stress plays a critical role in 308 glomerular dysfunction. Along with chronic inflammation, CD36 may facilitate the development 309 of oxidant stress in LN (Hua et al 2015, Kennedy et al 2013, Aliou et al 2016. 310 Podocyte is most susceptible to injury among the component of the glomerulus and its injury 311 leads to glomerular dysfunction in various renal diseases including LN.…”