Sex-dependent differences in the adverse renal changes induced by an early in life exposure to a high-fat diet

Abstract

This study examines whether the intake of a high-fat diet very early in life leads to changes in arterial pressure and renal function and evaluates whether the mechanisms involved in these changes are sex-dependent. Experiments were performed in male and female Sprague-Dawley rats fed a normal or high-fat diet from weaning to 4 mo of age. This exposure to a high-fat diet lead to an angiotensin II-dependent elevation in arterial pressure and to significant increments in fat abdominal volume and plasma leptin that were similar in both sexes. In addition, the angiotensin II-induced increment in renal vascular resistance was greater ( P < 0.05) in male (106 ± 14%) and female (97 ± 15%) rats fed a high-fat diet than in rats fed a normal-fat diet (51 ± 8%). However, the high-fat intake during early life induced increments in albuminuria, interleukin-6, and infiltration of CD3 lymphocytes in the renal parenchyma that were greater ( P < 0.05) in male than in female rats. Other sex-dependent differences in response to high-fat intake were that adiponectin levels only decreased in females (21%, P < 0.05), and renal NF-κB expression only increased in males (31%, P < 0.05). In summary, the early exposure to a high-fat diet leads to angiotensin II-dependent arterial pressure elevations and to increments in abdominal fat and in the renal sensitivity to angiotensin II that are similar in both sexes. However, the mechanisms involved in the renal changes associated with early exposure to a high-fat diet are different in males and females.

Cardiac, renal and uterine hemodynamics changes throughout pregnancy in rats with a prolonged high fat diet from an early age

“…Changes in leptin, adiponectin and inflammatory mediators have been proposed to be involved in the altered uteroplacental blood flow during pregnancy in obese subjects [21,31,40]. Taking together with those reported previously [12], our results suggest that an early and prolonged HFD may alter the intrauterine environment as a consequence of changes in adipokines and inflammatory mediators. An imbalance in the circulating levels of pro-(VEGF and PlGF) and anti-angiogenic (sFlt-1) factors could also be involved in the AP increment and in the altered renal and uterine hemodynamic changes during pregnancy in rats with an early and prolonged exposure to a HFD.…”

“…The absence of a significant elevation in GFR during most of gestation in rats with a prolonged HFD (Fig 5) is important since glomerular hyperfiltration allows eliminating the waste products of metabolism and it is consequently necessary to have a healthy pregnancy. The renal hemodynamic changes in rats fed a prolonged HFD may be related to the increments in interleukin-6, infiltration of T cells in the renal tissue, albuminuria and leptin levels, and to the decrease in adiponectin in these rats before pregnancy [12,39]. The reduced uteroplacental flow may also be related to the absence of a significant increment in GFR during the second and third week of pregnancy.…”

“…The importance of evaluating the impact of an early and prolonged HFD on the cardiac, renal and uterine hemodynamics changes during pregnancy is obvious because the offspring of dams with an early HFD may develop cardiovascular and metabolic dysfunctions at early ages [27][28][29]. The SAP elevation before pregnancy in rats with HFD (Fig 1) are associated to increases in fat abdominal volume and leptin, and a decrease in adiponectin [12]. Epidemiological and experimental studies showed that AP is elevated at the middle and at the end of gestation in obese subjects [30] but they did not examine whether AP was already elevated before pregnancy.…”

“…The hypothesis was that this prolonged HFD would lead to an altered vascular adaptation in organs that contribute to the decrease in total peripheral resistance and adequate fetal development during gestation. This hypothesis is supported by results showing that females with a HFD from weaning are hypertensive, have an elevation in leptin, a decrease in adiponectin levels, and an enhanced infiltration of lymphocytes in the kidney [12]. Cardiac, renal and uterine hemodynamic changes were assessed before and throughout gestation by non-invasive methods, in rats with normal (NFD) or high fat diets.…”

“…The calories in HFD (Tekland TD.06414, Energy density: 5.1 Kcal/g) are from proteins (18,4%), fat (lard + soybean oil) (60.3%) and carbohydrate (21.3%). Food intake was not measured but a previous study [12] showed that food intake was greater (p<0.05) in rats with NFD (15,3 ± 1,1 grams/day) than in rats with HFD (11,8 ± 1,4 grams/day) at 3,5 months of age.…”