Maternal High Fat Diet Alters Skeletal Muscle Mitochondrial Catalytic Activity in Adult Male Rat Offspring

Pileggi, Chantal; Hedges, Christopher P.; Segovia, Stephanie A.; Markworth, James F.; Durainayagam, Brenan R.; Gray, Charles M.; Zhang, Xiaoyuan D.; Barnett, Matthew P. G.; Vickers, Mark H.; Hickey, Anthony J. R.; Reynolds, Clare M.; Cameron‐Smith, David

doi:10.3389/fphys.2016.00546

Cited by 39 publications

(29 citation statements)

References 46 publications

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“…Mitofusin 1 and 2 (MFN 1 and 2) and OPA1 and DRP1 modulate fusion and fission processes, respectively, helping to reduce cellular stress by joining mitochondria or creating new mitochondria to assists deficient mitochondria [ 18 ]. Maternal programming by HFD exposure in rodent dams, decrease expression of OPA1 and DRP1 proteins in skeletal muscles of female offspring and disrupt mitochondrial function in male offspring [ 19 , 20 ], which might be transmitted across three generations [ 20 ]. Furthermore, we and others have reported that obese mice showed changes in MFN2 expression in hypothalamus and other tissues [ 21 – 24 ], and importantly mitochondria elongate in a Mfn1/2 dependent manner in Agouti-related peptide neurons [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Maternal overnutrition by hypercaloric diets programs hypothalamic mitochondrial fusion and metabolic dysfunction in rat male offspring

et al. 2018

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BackgroundMaternal overnutrition including pre-pregnancy, pregnancy and lactation promotes a lipotoxic insult leading to metabolic dysfunction in offspring. Diet-induced obesity models (DIO) show that changes in hypothalamic mitochondria fusion and fission dynamics modulate metabolic dysfunction. Using three selective diet formula including a High fat diet (HFD), Cafeteria (CAF) and High Sugar Diet (HSD), we hypothesized that maternal diets exposure program leads to selective changes in hypothalamic mitochondria fusion and fission dynamics in male offspring leading to metabolic dysfunction which is exacerbated by a second exposure after weaning.MethodsWe exposed female Wistar rats to nutritional programming including Chow, HFD, CAF, or HSD for 9 weeks (pre-mating, mating, pregnancy and lactation) or to the same diets to offspring after weaning. We determined body weight, food intake and metabolic parameters in the offspring from 21 to 60 days old. Hypothalamus was dissected at 60 days old to determine mitochondria-ER interaction markers by mRNA expression and western blot and morphology by transmission electron microscopy (TEM). Mitochondrial-ER function was analyzed by confocal microscopy using hypothalamic cell line mHypoA-CLU192.ResultsMaternal programming by HFD and CAF leads to failure in glucose, leptin and insulin sensitivity and fat accumulation. Additionally, HFD and CAF programming promote mitochondrial fusion by increasing the expression of MFN2 and decreasing DRP1, respectively. Further, TEM analysis confirms that CAF exposure after programing leads to an increase in mitochondria fusion and enhanced mitochondrial-ER interaction, which partially correlates with metabolic dysfunction and fat accumulation in the HFD and CAF groups. Finally, we identified that lipotoxic palmitic acid stimulus in hypothalamic cells increases Ca2+ overload into mitochondria matrix leading to mitochondrial dysfunction.ConclusionsWe concluded that maternal programming by HFD induces hypothalamic mitochondria fusion, metabolic dysfunction and fat accumulation in male offspring, which is exacerbated by HFD or CAF exposure after weaning, potentially due to mitochondria calcium overflux.

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Section: Introductionmentioning

confidence: 99%

Maternal overnutrition by hypercaloric diets programs hypothalamic mitochondrial fusion and metabolic dysfunction in rat male offspring

et al. 2018

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“…In humans, obese mothers have a greater probability of having obese offspring (Gale et al 2007). Similarly, a maternal high-fat diet (HFD) in rodents causes offspring insulin resistance (Nivoit et al 2009), hyperphagia and hypertension (Samuelsson et al 2008) in adulthood, as well as reduced skeletal muscle mitochondrial transcription factors and oxidative phosphorylation (Latouche et al 2014;Pileggi et al 2016).…”

Section: Introductionmentioning

confidence: 99%

Four weeks of exercise early in life reprograms adult skeletal muscle insulin resistance caused by a paternal high‐fat diet

Falcão-Tebas

Kuang

Arceri

et al. 2018

The Journal of Physiology

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Key points A paternal high‐fat diet/obesity before mating can negatively influence the metabolism of offspring. Exercise only early in life has a remarkable effect with respect to reprogramming adult rat offspring exposed to detrimental insults before conception. Exercise only early in life normalized adult whole body and muscle insulin resistance as a result of having a high‐fat fed/obese father. Unlike the effects on the muscle, early exercise did not normalize the reduced adult pancreatic beta cell mass as a result of having a high‐fat fed/obese father. Early‐life exercise training may be able to reprogram an individual whose father was obese, inducing long‐lasting beneficial effects on health. Abstract A paternal high‐fat diet (HFD) impairs female rat offspring glucose tolerance, pancreatic morphology and insulin secretion. We examined whether only 4 weeks of exercise early in life could reprogram these negative effects. Male Sprague–Dawley rats consumed a HFD for 10 weeks before mating with chow‐fed dams. Female offspring remained sedentary or performed moderate intensity treadmill exercise (5 days week−1, 60 min day−1, 20 m min−1) from 5 to 9 weeks of age. Paternal HFD impaired (P < 0.05) adult offspring whole body insulin sensitivity (i.p. insulin sensitivity test), as well as skeletal muscle ex vivo insulin sensitivity and TBC1D4 phosphorylation. It also lowered β‐cell mass and reduced in vivo insulin secretion in response to an i.p. glucose tolerance test. Early‐life exercise in offspring reprogrammed the negative effects of a paternal HFD on whole body insulin sensitivity, skeletal muscle ex vivo insulin‐stimulated glucose uptake and TBC1D4 phosphorylation and also increased glucose transporter 4 protein. However, early exercise did not normalize the reduced pancreatic β‐cell mass or insulin secretion. In conclusion, only 4 weeks of exercise early in life in female rat offspring reprograms reductions in insulin sensitivity in adulthood caused by a paternal HFD without affecting pancreatic β‐cell mass or insulin secretion.

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“…29 Muscle protein expression of respiratory chain complexes I-V is lower in offspring of mothers fed a HF diet, and bioinformatics revealed downregulation of pathways associated with oxidative phosphorylation (OXPHOS), electron transfer system (ETS) and adenosine triphosphate (ATP) synthesis. 24,30 Under these conditions, it is a strong possibility that OXPHOS capacity could be compromised. However, there is limited data on the impact of maternal obesity and postnatal diet on skeletal muscle mitochondrial function.…”

Section: Introductionmentioning

confidence: 99%

Sex-specific effects of maternal and postweaning high-fat diet on skeletal muscle mitochondrial respiration

Khamoui

Desai

Ross

et al. 2018

J Dev Orig Health Dis

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Exposure to maternal over-nutrition in utero is linked with developmental programming of obesity, metabolic syndrome and cardiovascular disease in offspring, which may be exacerbated by postnatal high-fat (HF) diet. Skeletal muscle mitochondrial function contributes to substrate metabolism and is impaired in metabolic disease. We examined muscle mitochondrial respiration in male and female mice exposed to maternal HF diet in utero, followed by postweaning HF diet until middle age. After in utero exposure to maternal control (Con) or HF diet (45% kcal fat; 39.4% lard, 5.5% soybean oil), offspring were weaned to Con or HF, creating four groups: Con/Con (male/female (m/f), n=8/8), Con/HF (m/f, n=7/4), HF/Con (m/f, n=9/6) and HF/HF (m/f, n=4/4). Oxidative phosphorylation (OXPHOS) and electron transfer system (ETS) capacity were measured in permeabilized gastrocnemius bundles. Maternal HF diet increased fasting glucose and lean body mass in males and body fat percentage in both sexes (P⩽0.05). Maximal adenosine diphosphate-stimulated respiration (complex I OXPHOS) was decreased by maternal HF diet in female offspring (-21%, P=0.053), but not in male (-0%, P>0.05). Sexually divergent responses were exacerbated in offspring weaned to HF diet. In females, OXPHOS capacity was lower (-28%, P=0.041) when weaned to high-fat (HF/HF) v. control diet (HF/Con). In males, OXPHOS (+33%, P=0.009) and ETS (+42%, P=0.016) capacity increased. Our data suggest that maternal lard-based HF diet, rich in saturated fat, affects offspring skeletal muscle respiration in a sex-dependent manner, and these differences are exacerbated by HF diet in adulthood.

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Maternal High Fat Diet Alters Skeletal Muscle Mitochondrial Catalytic Activity in Adult Male Rat Offspring

Cited by 39 publications

References 46 publications

Maternal overnutrition by hypercaloric diets programs hypothalamic mitochondrial fusion and metabolic dysfunction in rat male offspring

Maternal overnutrition by hypercaloric diets programs hypothalamic mitochondrial fusion and metabolic dysfunction in rat male offspring

Four weeks of exercise early in life reprograms adult skeletal muscle insulin resistance caused by a paternal high‐fat diet

Sex-specific effects of maternal and postweaning high-fat diet on skeletal muscle mitochondrial respiration

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