Ichthyosis, cataracts, and motor delay in an infant: A case of Chanarin-Dorfman syndrome.

Chanarin-Dorfman syndrome (CDS) is a rare, autosomal recessive disorder of impaired triacylglycerol catabolism leading to cytoplasmic deposition of triglycerides in various cell types. We describe the case of an 8-month-old boy with cataracts, strabismus, motor delays, and an ichthyosiform rash since birth. Genetic testing revealed a pathogenic variant of the ABHD5 gene, suggestive of CDS, and further workup demonstrated hepatic steatosis and myopathy. His ichthyosis improved with initiation of a diet low in very long-chain fatty acids and medium-chain fatty acid supplementation.

Enhanced Triacylglycerol Content and Gene Expression for Triacylglycerol Metabolism, Acyl-Ceramide Synthesis, and Corneocyte Lipid Formation in the Epidermis of Borage Oil Fed Guinea Pigs.

Triacylglycerol (TAG) metabolism is related to the acyl-ceramide (Cer) synthesis and corneocyte lipid envelope (CLE) formation involved in maintaining the epidermal barrier. Prompted by the recovery of a disrupted epidermal barrier with dietary borage oil (BO: 40.9% linoleic acid (LNA) and 24.0% γ-linolenic acid (GLA)) in essential fatty acid (EFA) deficiency, lipidomic and transcriptome analyses and subsequent quantitative RT-PCR were performed to determine the effects of borage oil (BO) on TAG content and species, and the gene expression related to overall lipid metabolism. Dietary BO for 2 weeks in EFA-deficient guinea pigs increased the total TAG content, including the TAG species esterified LNA, GLA, and their C20 metabolized fatty acids. Moreover, the expression levels of genes in the monoacylglycerol and glycerol-3-phosphate pathways, two major pathways of TAG synthesis, increased, along with those of TAG lipase, acyl-Cer synthesis, and CLE formation. Dietary BO enhanced TAG content, the gene expression of TAG metabolism, acyl-Cer synthesis, and CLE formation.

ABHD5 blunts the sensitivity of colorectal cancer to fluorouracil via promoting autophagic uracil yield.

The efficacy of Fluorouracil (FU) in the treatment of colorectal cancer (CRC) is greatly limited by drug resistance. Autophagy has been implicated in chemoresistance, but the role of selective autophagic degradation in regulating chemoresistance remains unknown. In this study, we revealed a critical role of ABHD5 in charging CRC sensitivity to FU via regulating autophagic uracil yield. We demonstrated that ABHD5 localizes to lysosome and interacts with PDIA5 to prevent PDIA5 from interacting with RNASET2 and inactivating RNASET2. ABHD5 deficiency releases PDIA5 to directly interact with RNASET2 and leave RNASET2 in an inactivate state, which impairs RNASET2-mediated autophagic uracil yield and promotes CRC cells to uptake FU as an exogenous uracil, thus increasing their sensitivity to FU. Our findings for the first time reveal a novel role of ABHD5 in regulating lysosome function, highlighting the significance of ABHD5 as a compelling biomarker predicting the sensitivity of CRCs to FU-based chemotherapy.

Role of 1-acyl-sn-glycerol-3-phosphate acyltransferase in psychrotrophy and stress tolerance of Serratia plymuthica RVH1.

A mutant with a transposon insertion just upstream of the lysophosphatidic acid acyltansferase gene plsC was isolated in a screen for mutants affected in growth at low temperature of the psychrotroph Serratia plymuthica RVH1. This mutant had lost its ability to grow at 4 °C and was severely affected in growth at 10 °C, but showed only slightly reduced growth at 30 °C. Fatty acid analysis of membrane extracts showed that the ratio of C16:1/C18:1 fatty acids was six-to sevenfold reduced in the mutant, although the ratio of unsaturated to saturated fatty acids was unaffected. The homeoviscous adaptation ability of the mutant was also unaffected. Growth and fatty acid composition were mostly restored by overexpressing plsC on a plasmid. Supplementation of C16:1 (palmitoleic acid) into the growth medium partially rescued low temperature growth, indicating that a balanced ratio of the two main unsaturated fatty acids is required for psychrotrophy. The mutant was significantly more strongly inactivated by high pressure treatment at 250 MPa, but not at higher pressures. It also showed reduced growth at low pH, but not at increased NaCl concentrations. This work provides novel information on the role of membrane fatty acid composition in stress tolerance.

Altered hypothalamic protein expression in a rat model of Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder, which is characterized by progressive motor impairment and cognitive alterations. Changes in energy metabolism, neuroendocrine function, body weight, euglycemia, appetite function, and circadian rhythm can also occur. It is likely that the locus of these alterations is the hypothalamus. We used the HD transgenic (tg) rat model bearing 51 CAG repeats, which exhibits similar HD symptomology as HD patients to investigate hypothalamic function. We conducted detailed hypothalamic proteome analyses and also measured circulating levels of various metabolic hormones and lipids in pre-symptomatic and symptomatic animals. Our results demonstrate that there are significant alterations in HD rat hypothalamic protein expression such as glial fibrillary acidic protein (GFAP), heat shock protein-70, the oxidative damage protein glutathione peroxidase (Gpx4), glycogen synthase1 (Gys1) and the lipid synthesis enzyme acylglycerol-3-phosphate O-acyltransferase 1 (Agpat1). In addition, there are significant alterations in various circulating metabolic hormones and lipids in pre-symptomatic animals including, insulin, leptin, triglycerides and HDL, before any motor or cognitive alterations are apparent. These early metabolic and lipid alterations are likely prodromal signs of hypothalamic dysfunction. Gaining a greater understanding of the hypothalamic and metabolic alterations that occur in HD, could lead to the development of novel therapeutics for early interventional treatment of HD.

Dietary trans fatty acid isomers differ in their effects on mammary lipid metabolism as well as lipogenic gene expression in lactating mice.

The biological activities and mechanisms of action of individual transoctadecenoic acids (trans-18:1 FA) have not been completely elucidated. We examined the effects of several individual trans-18:1 FA isomers and trans-10, cis-12 conjugated linoleic acid (CLA) on fat synthesis, and expression of lipogenic genes in mammary and liver tissue in lactating mice. From d 6 to 10 postpartum, 30 lactating C57BL/6J mice were randomly assigned to either a control (CTR) diet containing 20 g/kg oleic acid or diets in which the oleic acid was either completely replaced by partially hydrogenated vegetable oil (PHVO), trans-7 18:1 (T7), trans-9 18:1 (T9), or trans-11 18:1 (T11) or partially replaced with 6.66 g/kg trans-10, cis-12 CLA. Milk fat percentage was decreased by CLA (44%), T7 (27%), and PHVO (23%), compared with CTR. In the mammary gland, CLA decreased the expression of genes related to de novo FA synthesis, desaturation, triacylglycerol formation, and transcriptional regulation. PHVO and T7 diets decreased the expression of 1-acylglycerol-3-phosphate O-acyltransferase and thyroid hormone responsive SPOT14 homolog (THRSP) mRNA. In contrast, dietary trans FA (tFA) did not affect hepatic lipogenic gene expression. However, mice fed CLA, T7, and PHVO diets had increased liver weights due to hepatic steatosis. Trans-7 18:1 was extensively desaturated to trans-7, cis-9 CLA in mammary and liver tissues. Dietary trans-7 18:1 could lead to milk fat depression in lactating mice, possibly through its desaturation product trans-7, cis-9 CLA. Also, the differences between the effects of trans-10, cis-12 CLA and other tFA could be attributed to its effects on carbohydrate response element binding protein and PPARgamma, in addition to sterol regulatory element binding transcription factor 1c and THRSP.