Excess Linoleic Acid Increases Collagen I/III Ratio and "Stiffens" the Heart Muscle Following High Fat Diets.

Controversy exists on the benefits versus harms of n-6 polyunsaturated fatty acids (n-6 PUFA). Although n-6 PUFA demonstrates anti-atherosclerotic properties, survival following cardiac remodeling may be compromised. We hypothesized that n-6 PUFA like linoleic acid (LA) or other downstream PUFAs like γ-linolenic acid or arachidonic acid alter the transforming growth factor-ß (TGFß)-collagen axis in the heart. Excess dietary LA increased the collagen I/III ratio in the mouse myocardium, leading to cardiac "stiffening" characterized by impaired transmitral flow indicative of early diastolic dysfunction within 5 weeks. In vitro, LA under TGFß1 stimulation increased collagen I and lysyl oxidase (LOX), the enzyme that cross-links soluble collagen resulting in deposited collagen. Overexpression of fatty acid desaturase 2 (fads2), which metabolizes LA to downstream PUFAs, reduced collagen deposits, LOX maturation, and activity with LA, whereas overexpressing fads1, unrelated to LA desaturation, did not. Furthermore, fads2 knockdown by RNAi elevated LOX activity and collagen deposits in fibroblasts with LA but not oleic acid, implying a buildup of LA for aggravating such pro-fibrotic effects. As direct incubation with γ-linolenic acid or arachidonic acid also attenuated collagen deposits and LOX activity, we concluded that LA itself, independent of other downstream PUFAs, promotes the pro-fibrotic effects of n-6 PUFA. Overall, these results attempt to reconcile opposing views of n-6 PUFA on the cardiovascular system and present evidence supporting a cardiac muscle-specific effect of n-6 PUFAs. Therefore, aggravation of the collagen I/III ratio and cardiac stiffening by excess n-6 PUFA represent a novel pathway of cardiac lipotoxicity caused by high n-6 PUFA diets.

Aquaporin homologs and water transport in the anal papillae of the larval mosquito, Aedes aegypti.

The hemolymph osmolarity of the freshwater mosquito larvae (Aedes aegypti) is greater than that of their habitat. To combat the influx of water, larvae cycle water entering through the gut and anal papillae to the Malpighian tubules for secretion. The presence of aquaporins (AQPs, water channels) may facilitate the movement of water across these tissues. Tissue distribution of mRNA transcripts of putative aquaporins from mosquito larvae, using quantitative PCR, revealed expression of transcripts in the Malpighian tubules and anal papillae. Four putative aquaporin transcripts are expressed in the Malpighian tubules and provide a basis for further work aimed at discovering the elusive water transporters functioning during diuresis. Transcripts of putative AQPs (AaAQP4 and AaAQP1b) are expressed in the anal papillae. Immunoreactivity to a human AQP1-antibody was found in the anal papillae and mercury inhibits tritiated water uptake in isolated anal papillae. Together, the results suggest that AQP(s) could be responsible for facilitating water transport at the papillae epithelium.