Paternal High Fat Diet in Rats Leads to Renal Accumulation of Lipid and Tubular Changes in Adult Offspring

Abstract

Along with diabetes and obesity, chronic kidney disease (CKD) is increasing across the globe. Although some data support an effect of maternal obesity on offspring kidney, the impact of paternal obesity is unknown; thus, we have studied the effect of paternal obesity prior to conception. Male Sprague Dawley rats were fed chow diet or high fat diet (HFD) for 13–14 weeks before mating with chow-fed females. Male offspring were weaned onto chow and killed at 27 weeks for renal gene expression and histology. Fathers on HFD were 30% heavier than Controls at mating. At 27 weeks of age offspring of obese fathers weighed 10% less; kidney triglyceride content was significantly increased (5.35 ± 0.84 vs. 2.99 ± 0.47 μg/mg, p < 0.05, n = 8 litters per group. Histological analysis of the kidney demonstrated signs of tubule damage, with significantly greater loss of brush border, and increased cell sloughing in offspring of obese compared to Control fathers. Acat1, involved in entry of fatty acid for beta-oxidation, was significantly upregulated, possibly to counteract increased triglyceride storage. However other genes involved in lipid metabolism, inflammation and kidney injury showed no changes. Paternal obesity was associated with renal triglyceride accumulation and histological changes in tubules, suggesting a mild renal insult in offspring, who may be at risk of developing CKD.

Dietary Micronutrient Supplementation for 12 Days in Obese Male Mice Restores Sperm Oxidative Stress

“…These sperm traits were coupled with reduced live birth rates after assisted reproductive treatment [5]. Alarmingly, male obesity at conception can also impact the next generation, manifesting as altered birth weights in humans [6,7] and animal models [8,9,10,11,12,13], while also making offspring more susceptibility to metabolic syndrome [8,9,14], sub-fertility [15], fatty liver disease [16], kidney disease [17], and hypertension [18]. Therefore, there is a need for clinically applicable interventions in obese men prior to conception to help improve both sperm quality but to also break the transgenerational disease cycle.…”

Changes in urinary metabolome related to body fat involve intermediates of choline processing by gut microbiota

“…Potential change in renal function (nephropathy) reported in HFD-induced obese animals [11, 12], is unlikely to affect the results since other small molecule urinary metabolites showed no significant correlation with body fat (Table 3). In addition, the potential effect of variations in urine volume was excluded by normalizing metabolite levels to the corresponding urinary creatinine concentration in each individual animal.…”

A combination of monosodium glutamate and high-fat and high-fructose diets increases the risk of kidney injury, gut dysbiosis and host-microbial co-metabolism

“…Increased levels of blood uremic toxins such as p-cresol sulfate might cause kidney damage in our animal model as reflected by the greater amount of this metabolite in urine. A postulated mechanism of kidney injury is summarized in Fig 5. It is well known that consumption of MSG or a HFF diet has the potential to induce kidney injury, reflected in changing histology in kidney tissues [47][48][49]; however, there is no information on the effect of these in combination on kidney pathology. Here we present such information for the first time.…”