Maternal high-fat high-sucrose diet and gestational exercise modulate hepatic fat accumulation and liver mitochondrial respiratory capacity in mothers and male offspring

Abstract

Background: Maternal high-caloric nutrition and related gestational diabetes mellitus (GDM) are associated with a high-risk for developing metabolic complications later in life and in their offspring. In contrast, exercise is recognized as a non-pharmacological strategy against metabolic dysfunctions associated to lifestyle disorders. Therefore, we investigated whether gestational exercise delays the development of metabolic alterations in GDM mothers later in life, but also protects 6-week-old male offspring from adverse effects of maternal diet. Methods: Female Sprague-Dawley rats were fed with either control (C) or high-fat high-sucrose (HFHS) diet to induce GDM and submitted to gestational exercise during the 3 weeks of pregnancy. Male offspring were sedentary and fed with C-diet. Results: Sedentary HFHS-fed dams exhibited increased gestational body weight gain (p < 0.01) and glucose intolerance (p < 0.01), characteristic of GDM. Their offspring had normal glucose metabolism, but increased early-age body weight, which was reverted by gestational exercise. Gestational exercise also reduced offspring hepatic triglycerides accumulation (p < 0.05) and improved liver mitochondrial respiration capacity (p < 0.05), contributing to the recovery of liver bioenergetics compromised by maternal HFHS diet. Interestingly, liver mitochondrial respiration remained increased by gestational exercise in HFHS-fed dams despite prolonged HFHS consumption and exercise cessation. Conclusions: Gestational exercise can result in liver mitochondrial adaptations in GDM animals, which can be preserved even after the exercise program cessation. Exposure to maternal GDM programs liver metabolic setting of male offspring, whereas gestational exercise appears as an important preventive tool against maternal dietinduced metabolic alterations.

Exercise as a Therapeutic Intervention in Gestational Diabetes Mellitus

“…Importantly, the role of exercise training in preventing/minimizing the negative effects of maternal obesity and diabetic exposure in the offspring of GDM (i.e., reduce obesity, insulin resistance, and hepatic steatosis in the offspring) has been highlighted by recent studies in animals. Specifically, gestational exercise in GDM animals reduced offspring hepatic triglycerides accumulation and improved liver mitochondrial respiratory capacity [77]. These beneficial effects were preserved even after the cessation of the exercise training program.…”

Metabolic Disease Programming: From Mitochondria to Epigenetics, Glucocorticoid Signalling and Beyond

“…132 Interventions that impact mitochondria and oxidative stress, such as antioxidants consumption and gestational practice of physical exercise, could potentially revert deleterious foetal programming effects. [133][134][135][136] Mitochondrial dysregulation in early life due to maternal stress conditions could have severe consequences for the offspring later in life. Further studies are needed to clarify the mechanisms by which mitochondria are imprinted for future disease, depending on the tissue and maternal-induced intrauterine insult.…”

“…MO during pregnancy induced testicular and sperm oxidative stress in male offspring, as suggested by the elevated MDA levels and reduced SOD and GPx activities, which decreased the viability motility and induced more abnormalities in sperm, compromising fertility 132 . Interventions that impact mitochondria and oxidative stress, such as antioxidants consumption and gestational practice of physical exercise, could potentially revert deleterious foetal programming effects 133‐136 …”

Asupan Karbohidrat Harian terhadap Risiko Kejadian Diabetes Melitus Gestasi (GDM) melalui Glyco-Hemoglobin Ibu Hamil

“…Wanita dengan GDM memiliki peningkatan risiko morbiditas kehamilan, risiko sindroma hipertensi kehamilan, persalinan premature, persalinan dengan sesaria, trauma obstetric, peningkatan risiko IGT/Impaired Glucose Tollerant (gangguan toleransi glukosa), dan diabetes tipe-2 beberapa tahun setelah kehamilan. Anak dari wanita dengan GDM lebih cenderung mengalami peningkatan signifikan berat badan dan panjang badan fetus, gangguan metabolisme, hypoglycemia neonatal, obesitas dan berisiko IGT, serta diabetes pada usia dewasa awal nantinya (Rasmussen et al, 2020;Silva et al, 2021). Gestational diabetes mellitus (GDM) berpengaruh penting selama kehamilan (perinatal) karena memicu obesitas dan intoleransi glukosa kongenital (turunan).…”

“…Mendiagnosis GDM secara tepat dapat menurunkan komplikasi perinatal, tetapi hanya sedikit faktor risiko dapat dihindari. Tes glukosa segera dapat menstratifikasi risiko diabetes jangka pendek dan selanjutnya uji glukosahemoglobin HbA1c dapat mendeteksi kontrol glikemia dari asupan karbohidrat yang memburuk sebagai penanda diabetes mellitus lanjutan (diabetes tipe-2) maupun diabetes kehamilan (Silva et al, 2021).…”