In the presence of dietary lipids, both apolipoprotein A-IV (ApoA-IV) production and brown adipose tissue (BAT) thermogenesis are increased. The effect of dietary lipid-induced AproA-IV on BAT thermogenesis and energy expenditure remains unknown. In the present study, we hypothesized that ApoA-IV knockout (ApoA-IV-KO) mice exhibited decreased BAT thermogenesis to affect energy homeostasis. To test this hypothesis, BAT thermogenesis in wildtype (WT) and ApoA-IV-KO mice fed either a standard low-fat chow diet or a high-fat diet (HFD) was investigated. When fed a chow diet, energy expenditure and food intake were comparable between WT and ApoA-IV-KO mice. After 1 week of HFD consumption, ApoA-IV-KO mice had comparable energy intake but produced lower energy expenditure relative to their WT controls in the dark phase. After an acute feeding of dietary lipids or 1-week HFD feeding, ApoA-IV-KO mice produced lower levels of uncoupling protein 1 (UCP1) and exhibited reduced expression of thermogenic genes in the BAT compared with WT controls. In response to cold exposure, however, ApoA-IV-KO mice had comparable energy expenditure and BAT temperature relative to WT mice. Thus, ApoA-IV-KO mice exhibited reduced diet-induced BAT thermogenesis and energy expenditure.

Stimulation of thermogenesis in brown adipose tissue (BAT) could have far-reaching health benefits in combatting obesity and obesity-related complications. Apolipoprotein A-IV (ApoA-IV), produced by the gut and the brain in the presence of dietary lipids, is a well-known short-term satiating protein. While our previous studies have demonstrated reduced diet-induced thermogenesis in ApoA-IV-deficient mice, it is unclear whether this reduction is due to a loss of peripheral or central effects of ApoA-IV. We hypothesized that central administration of ApoA-IV stimulates BAT thermogenesis and that sympathetic and sensory innervation is necessary for this action. To test this hypothesis, mice with unilateral denervation of interscapular BAT received central injections of recombinant ApoA-IV protein or artificial cerebrospinal fluid (CSF). The effects of central ApoA-IV on BAT temperature and thermogenesis in mice with unilateral denervation of the intrascapular BAT were monitored using transponder probe implantation, qPCR, and immunoblots. Relative to CSF, central administration of ApoA-IV significantly increased temperature and UCP expression in BAT. However, all of these effects were significantly attenuated or prevented in mice with unilateral denervation. Together, these results clearly demonstrate that ApoA-IV regulates BAT thermogenesis centrally, and this effect is mediated through sympathetic and sensory nerves.

Background: Advanced stages of ovarian clear cell carcinoma have poorer prognoses than many other ovarian cancers. When standard treatments are ineffective, alternative options are needed. Case: A 56‐year‐old woman was diagnosed with ovarian clear cell carcinoma and treated with surgical management as well as carboplatin and paclitaxel. At recurrence, her disease progressed despite multiple chemotherapy regimens. A durable response was achieved first with alpelisib, chosen based on genomic testing. When progression occurred on this agent, a partial disease response was achieved with the combination of nivolumab and ipilimumab. Conclusion: The use of targeted therapies as well as the combination of nivolumab and ipilimumab is a promising option in advanced and recurrent cases of ovarian clear cell carcinoma.

Objective: To determine the effectiveness and tolerability of PARPi maintenance in a real-world patient population. Specifically, to assess duration of PARPi, the rate of secondary malignancies, rate of side effects, and survival. Methods: A retrospective review of patients with ovarian, fallopian tube, and primary peritoneal cancer at OhioHealth Riverside Methodist Hospital in Columbus, Ohio was performed. All patients diagnosed since March 2015 were reviewed for eligibility. Data was collected via EMR query and stored in REDCap. Charts were reviewed for multiple data points, including duration of PARPi use, side effects, secondary malignancies, survival, and recurrence. Data were reported descriptively with medians and ranges. Results: Ninety-seven patients met inclusion criteria. The median time patients were maintained on a PARPi was 9.8 months. Termination of patient’s PARPi was most often due to recurrence followed by side effects. Fatigue, anemia, and thrombocytopenia were the most common side effects reported. We report a PFS median of 12.5 months and a median OS of 40.6 months following first PARPi exposure. When stratified by homologous recombination deficiency (HRD) status, unadjusted analyses demonstrated longer PFS among HRD-positive patients compared to HRD-negative and HRD-unknown groups; however, this association was not consistently maintained after multivariable adjustment, and no statistically significant difference in OS was observed. There were two secondary malignancies identified in our study. Conclusions: We report similar survival compared to published trials despite shorter courses of therapy and higher rates of discontinuation due to side effects. Although HRD-positive status was associated with improved outcomes in unadjusted analyses, this effect was not sustained after adjustment for confounding variables, underscoring the complexity of these associations in real-world populations. This cohort study emphasizes the need to examine the real-world population for accurate patient guidance and counseling.