Switching to a Standard Chow Diet at Weaning Improves the Effects of Maternal and Postnatal High-Fat and High-Sucrose Diet on Cardiometabolic Health in Adult Male Mouse Offspring

Abstract

Cardiac mitochondrial dysfunction contributes to obesity-associated heart disease. Maternal and postnatal diet plays an important role in cardiac function, yet the impacts of a mismatch between prenatal and postweaning diet on cardiometabolic function are not well understood. We tested the hypothesis that switching to a standard chow diet after weaning would attenuate systemic metabolic disorders and cardiac and mitochondrial dysfunction associated with maternal and postnatal high-fat/high-sucrose (HFHS) diet in mice. Six-month-old male CD1 offspring from dams fed a HFHS diet and weaned to the same HFHS diet (HH) or switched to a standard chow diet (HC) were compared to offspring from dams fed a low-fat/low-sucrose diet and maintained on the same diet (LL). HC did not decrease body weight (BW) but normalized glucose tolerance, plasma cholesterol, LDL, and insulin levels compared to the HH. Systolic function indicated by the percent fractional shortening was not altered by diet. In freshly isolated cardiac mitochondria, maximal oxidative phosphorylation-linked respiratory capacity and coupling efficiency were significantly higher in the HC in the presence of fatty acid substrate compared to LL and HH, with modification of genes associated with metabolism and mitochondrial function. Switching to a standard chow diet at weaning can attenuate the deleterious effects of long-term HFHS in adult male mouse offspring.

Voluntary Wheel Running Reduces Cardiometabolic Risks in Female Offspring Exposed to Lifelong High-Fat, High-Sucrose Diet

“…Assessment of mitochondrial respiratory function. Mitochondrial respiratory function of the left ventricle was assessed using high-resolution respirometry (Oxygraph-2k; Oroboros Instruments, Innsbruck, Austria) on the freshly isolated mitochondria (30 mg) in a manner previously described, although with some adjustments (31,32). Briefly, 1 mM malate and 5 mM pyruvate (PM) were sequentially added for the carbohydrate-focused protocol, followed by 2.5 mM Adenosine diphosphate (ADP), 10 mM glutamate, and 20 mM succinate.…”

Made in the Womb: Maternal Programming of Offspring Cardiovascular Function by an Obesogenic Womb

“…Therefore, changes in cardiac metabolism have been linked to oxidative stress, mitochondrial dysfunction, and mitophagy [ 162 ]. Proposed mechanisms for mitochondrial dysfunction include mitochondrial structural adaptations (cristae effacement) [ 193 , 194 ], impairment in electron transport chain (ETC) complex activities, defects in the assembly and organization of OXPHOS supercomplexes, oxidative stress, decreased expression of cardiolipin, impaired TCA cycle anaplerosis, and mitochondrial uncoupling [ 195 ].…”

“…In 7-day-old mice offspring exposed to MO, cardiac SOD and reduced glutathione (GSH) and glutathione peroxidase (GPx) activities were decreased both in males and in females [ 199 ]. Interestingly, the LV tissue of mice offspring born to mothers given an HFHS diet presented increased levels of SOD2 in comparison with the control [ 195 ]. This is possibly in response to oxidative damage (especially lipid peroxidation) through increased levels of MDA in these offspring [ 195 ].…”

“…Interestingly, the LV tissue of mice offspring born to mothers given an HFHS diet presented increased levels of SOD2 in comparison with the control [ 195 ]. This is possibly in response to oxidative damage (especially lipid peroxidation) through increased levels of MDA in these offspring [ 195 ]. In fact, MDA was increased in cardiomyocytes of newborn Sprague Dawley MO rats [ 162 ].…”

Nurturing through Nutrition: Exploring the Role of Antioxidants in Maternal Diet during Pregnancy to Mitigate Developmental Programming of Chronic Diseases

“…Therefore, we consider it essential to investigate the pathways involved in these mechanisms, given their significant role in mitochondrial fitness [59]. Mitochondrial alterations in MO's offspring were also described in other tissues, namely in murine [60][61][62][63][64][65][66] and non-human primate studies [67], reporting alterations in the offspring's cardiac tissue [60][61][62]64], skeletal muscle [63,67], and hypothalamus [65]. Importantly, the majority of these studies consistently report impaired mitochondrial oxygen consumption across various time points in the offspring's life.…”