👤 Ron Sarver

C1q/TNF-related protein (CTRP) family comprises fifteen highly conserved secretory proteins with diverse central and peripheral functions. In zebrafish, mouse, and human, CTRP4 is most highly expressed in the brain. We previously showed that CTRP4 is a metabolically responsive regulator of food intake and energy balance, and mice lacking CTRP4 exhibit sexually dimorphic changes in ingestive behaviors and systemic metabolism. Recent single-cell RNA sequencing also revealed Ctrp4/C1qtnf4 expression in diverse neuronal cell types across distinct anatomical brain regions, hinting at additional roles in the central nervous system not previously characterized. To uncover additional central functions of CTRP4, we subjected Ctrp4 knockout (KO) mice to a battery of behavioral tests. Relative to wild-type (WT) littermates, loss of CTRP4 does not alter exploratory, anxiety-, or depressive-like behaviors, motor function and balance, sensorimotor gating, novel object recognition, and spatial memory. While pain-sensing mechanisms in response to thermal stress and mild shock are intact, both male and female Ctrp4 KO mice have increased sensitivity to pain induced by higher-level shock, suggesting altered nociceptive function. Importantly, CTRP4 deficiency impairs hippocampal-dependent associative learning and memory as assessed by trace fear conditioning paradigm. This deficit is sex-dependent, affects only female mice, and is associated with altered expression of learning and memory genes (Arc, c-fos, and Pde4d) in the hippocampus and cortex. Altogether, our behavioral and gene expression analyses have uncovered novel aspects of the CTRP4 function and provided a physiological context to further investigate its mechanism of action in the central and peripheral nervous system. Show less

Central and peripheral mechanisms are both required for proper control of energy homeostasis. Among circulating plasma proteins, C1q/TNF-related proteins (CTRPs) have recently emerged as important regulators of sugar and fat metabolism. CTRP4, expressed in brain and adipose tissue, is unique among the family members in having two tandem globular C1q domains. We previously showed that central administration of recombinant CTRP4 suppresses food intake, suggesting a central nervous system role in regulating ingestive physiology. Whether this effect is pharmacological or physiological remains unclear. We used a loss-of-function knockout (KO) mouse model to clarify the physiological role of CTRP4. Under basal conditions, CTRP4 deficiency increased serum cholesterol levels and impaired glucose tolerance in male but not female mice fed a control low-fat diet. When challenged with a high-fat diet, male and female KO mice responded differently to weight gain and had different food intake patterns. On an obesogenic diet, male KO mice had similar weight gain as wild-type littermates. When fed ad libitum, KO male mice had greater meal number, shorter intermeal interval, and reduced satiety ratio. Female KO mice, in contrast, had lower body weight and adiposity. In the refeeding period following food deprivation, female KO mice had significantly higher food intake due to longer meal duration and reduced satiety ratio. Collectively, our data provide genetic evidence for a sex-dependent physiological role of CTRP4 in modulating food intake patterns and systemic energy metabolism. Show less

A study was carried out to determine the efficacy of the Soleris Direct Yeast and Mold (DYM) automated growth-based method for semiquantitative detection of yeast and mold in a variety of food products. A probability of detection (POD) statistical model was used to compare Soleris results at multiple test thresholds (dilutions) with plate counts determined using the U.S. Food and Drug Administration Bacteriological Analytical Manual, Chapter 18, dilution plating procedure. Fourteen naturally contaminated food products were tested, with Soleris testing performed at three or more threshold levels for each food. Using the POD model, the majority of Soleris test results were in statistical agreement with the reference plating procedures. The exceptions included a single threshold level in yogurt, black pepper, dried fruit, and dry pet food, and two levels in nonfat dry milk and saw palmetto powder. In all but one of these instances, the exception being pet food, the statistical disagreement was due to Soleris estimating a higher level of contamination than the reference method. Results of ruggedness testing showed that the Soleris method produced accurate results even when significant variances in a critical operating parameter, incubation temperature, were introduced. Results of the internal and independent laboratory validation studies showed that the Soleris DYM method can be used as an accurate alternative to conventional dilution plating procedures for evaluation of yeast and mold counts at threshold levels, while saving as much as 72 h in analysis time. Show less