Obesity and Energy Substrate Transporters in Ovarian Cancer—Review

Ovarian cancer is the seventh most common cancer in women. It is characterized by a high mortality rate because of its aggressiveness and advanced stage at the time of diagnosis. It is a nonhomogenous group of neoplasms and, of which the molecular basics are still being investigated. Nowadays, the golden standard in the treatment is debulking cytoreductive surgery combined with platinum-based chemotherapy. We have presented the interactions and the resulting perspectives between fatty acid transporters, glucose transporters and ovarian cancer cells. Studies have shown the association between a lipid-rich environment and cancer progression, which suggests the use of correspondent transporter inhibitors as promising chemotherapeutic agents. This review summarizes preclinical and clinical studies highlighting the role of fatty acid transport proteins and glucose transporters in development, growth, metastasizing and its potential use in targeted therapies of ovarian cancer.

The effect of high glucose on lipid metabolism in the human placenta

Diabetes mellitus (DM) during pregnancy can result in fetal overgrowth, likely due to placental dysfunction, which has health consequences for the infant. Here we test our prediction from previous work using a placental cell line that high glucose concentrations affect placental lipid metabolism. Placentas from women with type 1 (n = 13), type 2 (n = 6) or gestational (n = 12) DM, BMI-matched to mothers without DM (n = 18), were analysed for lipase and fatty acid transport proteins and fatty acid and triglyceride content. Explants from uncomplicated pregnancies (n = 6) cultured in physiological or high glucose were similarly analysed. High glucose levels did not alter placental lipase or transporter expression or the profile and abundance of fatty acids, but triglyceride levels were higher (p < 0.05), suggesting reduced β- oxidation. DM did not affect placental protein expression or fatty acid profile. Triglyceride levels of placentas from mothers with pre-existing DM were similar to controls, but higher in obese women with gestational DM. Maternal hyperglycemia may not affect placental fatty acid uptake and transport. However, placental β-oxidation is affected by high glucose and reduced in a subset of women with DM. Abnormal placental lipid metabolism could contribute to increased maternal-fetal lipid transfer and excess fetal growth in some DM pregnancies.

Omega-3 fatty acids transport through the placenta

The placenta is a temporary vital organ for sustaining the development of the fetus throughout gestation. Although the fatty acid composition delivered to the fetus is largely determined by maternal circulating levels, the placenta preferentially transfers physiologically important long-chain polyunsaturated fatty acids (LC-PUFAs), particularly omega-3 (n-3) FAs. The precise mechanisms governing these transfers were covered in a veil, but have started to be revealed gradually. Several evidences suggest fatty acid transport proteins (FATPs), placental specific membrane bound fatty acid binding proteins (pFABPpm) and fatty acid translocases (FAT/CD36) involved in LC-PUFAs uptake. Our studies have shown that the placental transfer of omega-3 FAs through the trophoblast cells is largely contributed by fatty acid binding protein 3 (FABP3). Recently there are considerable interests in the potential for dietary omega-3 FAs as a therapeutic intervention for fetal disorders. In fact, prenatal supply of omega-3 FAs is essential for brain and retinal development. Recent findings suggest a potential opportunity of omega-3 FA interventions to decrease the incidence of type 2 diabetes in future generations. In this review, we discuss the molecular mechanism of transportation of omega-3 FAs through the placenta and how omega-3 FAs deficiency/supplementation impact on fetal development.Asian J. Med. Biol. Res. March 2016, 2(1): 1-8

Fatty acid transport proteins: targeting FATP2 as a gatekeeper involved in the transport of exogenous fatty acids

FATP2 as the gatekeeper (A), dysregulation of fatty acid metabolism from FA overload (B), and Lipofermata or Grassofermata treatment (C).