Fatty acid-mediated signaling as a target for developing type 1 diabetes therapies.

INTRODUCTION: Type 1 diabetes (T1D) is an autoimmune disease in which pro-inflammatory and cytotoxic signaling drive the death of the insulin-producing ß cells. This complex signaling is regulated in part by fatty acids and their bioproducts, making them excellent therapeutic targets. AREAS COVERED: We provide an overview of the fatty acid actions on ß cells by discussing how they can cause lipotoxicity or regulate inflammatory response during insulitis. We also discuss how diet can affect the availability of fatty acids and disease development. Finally, we discuss development avenues that need further exploration. EXPERT OPINION: Fatty acids, such as hydroxyl fatty acids, ω-3 fatty acids, and their downstream products, are druggable candidates that promote protective signaling. Inhibitors and antagonists of enzymes and receptors of arachidonic acid and free fatty acids, along with their derived metabolites, which cause pro-inflammatory and cytotoxic responses, have the potential to be developed as therapeutic targets also. Further, because diet is the main source of fatty acid intake in humans, balancing protective and pro-inflammatory/cytotoxic fatty acid levels through dietary therapy may have beneficial effects, delaying T1D progression. Therefore, therapeutic interventions targeting fatty acid signaling hold potential as avenues to treat T1D.

High-fat diet-induced dysregulation of ovarian gene expression is restored with chronic omega-3 fatty acid supplementation.

Chronic high-fat diet (HFD) consumption causes ovarian dysfunction in rodents. Acute dietary treatment with docosahexaenoic acid (DHA) increases oocyte quality and ovarian reserve at advanced reproductive age. We hypothesized that DHA supplementation after HFD exposure reverses HFD-induced ovarian defects. We conducted a dietary intervention with reversal to chow, DHA-supplemented chow, or DHA-supplemented HFD after HFD consumption. After 10 weeks, HFD-fed mice had impaired estrous cyclicity, decreased primordial follicles, and altered ovarian expression of 24 genes compared to chow controls. Diet reversal to either chow or chow + DHA restored estrous cyclicity, however only chow + DHA appeared to mitigated the impact of HFD on ovarian reserve. All dietary interventions restored HFD-dysregulated gene expression to chow levels. We found no association between follicular fluid DHA levels and ovarian reserve. In conclusion our data suggest some benefit of DHA supplementation after HFD, particularly in regards to ovarian gene expression, however complete restoration of ovarian function was not achieved.

The Role of Talker Familiarity in Auditory Distraction.

The current research employed a classic irrelevant sound effect paradigm and investigated the talker-specific content of the irrelevant speech. Specifically, we aimed to determine if the participants' familiarity with the irrelevant speech's talker affected the magnitude of the irrelevant sound effect. Experiment 1 was an exploration of talker familiarity established in a natural listening environment (i.e., a university classroom) in which we manipulated the participants' relationships with the talker. In Experiment 2, we manipulated the participants' familiarity with the talker via 4 days of controlled exposure to the target talker's audio recordings. For both Experiments 1 and 2, a robust effect of irrelevant speech was found; however, regardless of the talker manipulation, talker familiarity did not influence the size of the effect. We interpreted the results within the processing view of the auditory distraction effect and highlighted the notion that talker familiarity may be more vulnerable than once thought.