Gender Differences in Cardiac Remodeling Induced by a High-Fat Diet and Lifelong, Low-Dose Cadmium Exposure

Abstract

Childhood obesity, which is prevalent in developed countries, is a metabolic risk factor for cardiovascular disease. Cadmium (Cd), a ubiquitous environmental toxic metal, also has deleterious effects on the cardiovascular system. However, the combined effects of a high-fat diet (HFD) and lifelong, low-dose Cd exposure on cardiac remodeling remain unclear. This study aims to determine the effects of combined HFD and Cd exposure on cardiac remodeling, as well as gender-specific differences in the response. C57BL/6J mice were exposed to Cd at a low dose (L-Cd, 0.5 ppm) or high dose (H-Cd, 5 ppm) via drinking water from conception to sacrifice. After being weaned, the offspring mice were fed with a HFD (42% kcal from fat) for an additional 10 weeks. H-Cd exposure significantly increased Cd accumulation in the hearts of both parents and their offspring; a HFD showed no added effects on cardiac Cd content. H-Cd exposure increased cardiac metallothionein protein levels only in female mice, regardless of dietary intake. Histological analysis revealed that H-Cd exposure combined with a HFD induced cardiac hypertrophy and fibrosis only in female mice. This was further supported by elevated expression of ANP and COL1A1 protein levels along with COL1A1, COL1A2, and COL3A1 mRNA levels. Profibrotic markers PAI-1, CTGF, and FN were also elevated in HFD/H-Cd-exposed female mice. Levels of the oxidative stress marker 3-NT significantly increased in the hearts of HFD-fed female mice, whereas Cd exposure showed no additional effects. Of all the antioxidant markers examined, levels of CAT significantly increased in mice fed a HFD, regardless of gender and Cd exposure. In summary, a HFD combined with lifelong, low-dose Cd exposure induces cardiac hypertrophy and fibrosis in female but not male mice, a response that is independent of oxidative stress.

Chronic Cadmium Exposure Alters Cardiac Matrix Metalloproteinases in the Heart of Sprague-Dawley Rat

“…However, another pathway is the simultaneous implication of inflammation with oxidative stress during cadmium exposure ( Liu et al, 2015 ; Kukongviriyapan et al, 2016 ; Tucovic et al, 2018 ; Koopsamy Naidoo et al, 2019 ). Previous work has linked cadmium-induced oxidative stress with cardiovascular pathologies in both humans and animals ( Lee et al, 2006 ; Ferramola et al, 2011 ; Ferramola et al, 2012 ; Liang et al, 2019 ). A prior study using similar experimental conditions of 15 ppm for 8 weeks has reported the histopathological alterations in the heart of male Wistar rats in correlation with circulating inflammatory markers ( Yazihan et al, 2011a ).…”

Effect of cadmium administration on the antioxidant system and neuronal death in the hippocampus of rats

“…However, no previous reports relate brain Cd‐accumulation with a 3‐NT increase, at least in our knowledge. Although, high 3‐NT levels have been reported in different tissues after chronic exposure at low Cd concentrations in the kidney (Wang et al, 2013), heart (Liang et al, 2019), and liver (Varoni et al, 2017).…”

Effect of Cadmium on Children's Health in Prenatal and Postnatal Periods of Development

“…Отримані дані свідчили про те, що Cd взаємодіє з ВВЖ, змінюючи гомеостаз основних металів в печінці та нирках. Це явище, яке може робити внесок в основний механізм, відповідальний за розвиток пов'язаних з ожирінням патологій у багатьох органах [36]. Пренатальний вплив Cd був негативно пов'язаний з показниками абдомінального і периферичного ожиріння у дівчаток, але не у хлопчиків.…”