The impact of gestational diabetes and gestational hypertension on future cardiovascular events: A nationwide cross-sectional cohort study.

OBJECTIVES: Cardiovascular disease is the leading cause of female death worldwide. The link between future cardiovascular events and a history of hypertensive disease in pregnancy or gestational diabetes (GDM) has been well established. Less well understood is the impact on future cardiovascular risk when gestational hypertension (GH) and GDM have occurred together. We assessed the association of GDM and GH with future cardiovascular events both alone and in combination. STUDY DESIGN: All female patients discharged from French hospitals in 2013 with 5 years of subsequent and complete follow-up were identified. They were grouped depending on their history of GDM, history of GH, history of both or history of neither. After propensity score matching, patients with GDM and/or GH were matched 1:1 with patients with no GDM or GH. Hazard ratios (HR) for cardiovascular events during follow-up were adjusted by age at baseline. RESULTS: Women with a history of GH had an increased risk of cardiovascular death (HR 5.46, 95 % confidence interval [CI] 1.93-15.49). Women with a history of GDM had no significant difference in the risk of cardiovascular events such as myocardial infarction (HR 0.88, 95 %CI 0.38-2.03) and cardiovascular death (HR 1.25, 95 %CI 0.47-3.36) during the 5 year follow up. Those with a history of both GDM and GH had a significantly increased risk of myocardial infarction (HR 23.33, 95 %CI 4.84-112.39). CONCLUSION: Women with a history of both GH and GDM are at a 23-fold increased risk of myocardial infarction within the first 5 years of their postnatal lives.

Regulation of hepatic mitochondrial metabolism in response to a high fat diet: a longitudinal study in rats

Mitochondrial dysfunctions have been detected in non-alcoholic steatohepatitis, but less information exists regarding adaptation of mitochondrial function during the initiation of hepatic steatosis. This study aimed to determine in rat liver the sequence of mitochondrial and metabolic adaptations occurring during the first 8 weeks of a moderate high fat diet (HFD). Sprague-Dawley rats were fed a HFD during 2, 4, and 8 weeks. Mitochondrial oxygen consumption, respiratory chain complexes activity, and oxidative phosphorylation efficiency were assessed in isolated liver mitochondria. Gene expression related to fat metabolism and mitochondrial biogenesis were determined. Results were compared to data collected in a group of rats sacrificed before starting the HFD feeding. After 2 and 4 weeks of HFD, there was a development of fatty liver and a concomitant increase the expression of mitochondrial glycerol-3-phosphate acyltransferase (mtGPAT) and peroxisome proliferator-activated receptor Gammma. Higher serum Beta-hydroxybutyrate levels and enhanced hepatic pyruvate dehydrogenase kinase 4 expression suggested increased fatty acid oxidation. However, mitochondrial respiration and respiratory chain activity were normal. After 8 weeks of HFD, lower accumulation of liver triglycerides was associated with reduced expression of mtGPAT. At this time, oxygen consumption with palmitoyl-L-carnitine was decreased whereas oxidative phosphorylation efficiency (ATP/O) with succinate was enhanced. Hepatic levels of mtDNA were unchanged whatever the time points. This longitudinal study in rats fed a HFD showed that hepatic lipid homeostasis and mitochondrial function can adapt to face the increase in fatty acid availability (AU)

Dynamic regulation of mitochondrial network and oxidative functions during 3T3-L1 fat cell differentiation

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Mitochondria have been shown to be impaired in insulin resistance-related diseases but have not been extensively studied during the first steps of adipose cell development. This study was designed to determine the sequence of changes of the mitochondrial network and function during the first days of adipogenesis. 3T3-L1 preadipocytes were differentiated into adipocytes without using glitazone compounds. At days 0, 3, 6, 9, and 12, mitochondrial network imaging, mitochondrial oxygen consumption, membrane potential, and oxidative phosphorylation efficiency were assessed in permeabilized cells. Gene and protein expressions related to fatty acid metabolism and mitochondrial network were also determined. Compared to preadipocytes (day 0), new adipocytes (days 6 and 9) displayed profound (..) (AU)