👤 Francesco Alessandro Palermo

Efficient utilization of complex biomass-derived sugars and tolerance to inhibitors are key requirements for the viability of lignocellulosic-based biorefineries. In this study, a two-stage evolution of an industrial yeast strain engineered with a xylose isomerase pathway yielded strain AceY.14, which exhibited improved fermentative performance and increased tolerance to acetic acid. Whole-genome sequencing of the evolved strain identified SNPs in ZWF1, a component of the pentose phosphate pathway (PPP), and in the G1 cyclin gene CLN3, both of which were functionally validated through CRISPR and reverse engineering. The zwf1 Show less

Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder caused by mutations in genes regulating lipoprotein lipase activity, typically manifesting early in life. We describe a 70-year-old man with severe refractory hypertriglyceridemia, chronic hyperCKemia, and protein-energy malnutrition, ultimately diagnosed with FCS due to a homozygous pathogenic LPL variant (c.844G>T; p.Glu282*). Despite long-standing disease and comorbidities, treatment with volanesorsen, an antisense oligonucleotide targeting apolipoprotein C-III mRNA, produced a 74% reduction in triglyceride levels and marked clinical improvement. This case underscores that FCS may remain undetected until late adulthood, particularly when confounded by diabetes or chronic kidney disease. Recognition of characteristic biochemical profiles and family history is essential to avoid diagnostic delay and prevent irreversible pancreatic damage and malnutrition. Even in elderly patients, targeted therapy can substantially improve metabolic control and quality of life. Show less

The development of novel sophisticated medications that induce weight loss has revolutionized the management of people living with obesity (PwO). However, when body weight is reduced, muscle and bone are lost along with fat. In the present review, we quote and discuss existing evidence on the effects of the major anti-obesity medications on bone metabolism. Glucagon-like peptide-1 receptor (GLP-1R) agonists have shown a positive impact in preclinical studies but a neutral or negative, albeit not clinically significant, effect on bone turnover markers and bone mineral density in clinical studies. Nevertheless, fracture risk does not seem to increase with GLP-1R agonists use, at least in clinically relevant doses. Limited, mostly preclinical, data suggest that other incretin analogues, including dual GLP-1R and glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) agonists, dual GLP-1R and glucagon receptor (GCGR) agonists, and triple GLP-1R, GIPR and GCGR agonists, may have a positive effect on bone. Preclinical data with amylin analogues imply the same. Activin type II receptor (ActRII) antagonists may combine anti-obesity effects with simultaneous muscle and bone mass preservation and could be used either as monotherapy or in combination with incretin analogues. The bone effects of opioid receptor antagonists and setmelanotide are largely unknown, while the impact of the combination of phentermine with topiramate is assumed to be negative. Finally, very limited clinical evidence suggests that orlistat may have a neutral effect on bone metabolism. Show less

The regulation of sleep and metabolism are highly interconnected, and dysregulation of sleep is linked to metabolic diseases that include obesity, diabetes, and heart disease. Furthermore, both acute and long-term changes in diet potently impact sleep duration and quality. To identify novel factors that modulate interactions between sleep and metabolic state, we performed a genetic screen for their roles in regulating sleep duration, starvation resistance, and starvation-dependent modulation of sleep. This screen identified a number of genes with potential roles in regulating sleep, metabolism, or both processes. One such gene encodes the auxiliary ion channel UNC79, which was implicated in both the regulation of sleep and starvation resistance. Genetic knockdown or mutation of unc79 results in flies with increased sleep duration, as well as increased starvation resistance. Previous findings have shown that unc79 is required in pacemaker for 24-hours circadian rhythms. Here, we find that unc79 functions in the mushroom body, but not pacemaker neurons, to regulate sleep duration and starvation resistance. Together, these findings reveal spatially localized separable functions of unc79 in the regulation of circadian behavior, sleep, and metabolic function. Show less

Liver X receptor is a ligand-activated transcription factor, which is mainly involved in cholesterol homeostasis, bile acid and triglycerides metabolism, and, as recently discovered, in the glucose metabolism by direct regulation of liver glucokinase. Its modulation by exogenous factors, such as drugs, industrial by-products, and chemicals is documented. Owing to the abundance of these synthetic molecules in the environment, and to the established target role of this receptor, a number of representative compounds of phthalate, organophosphate and fibrate classes were tested as ligands/modulators of human liver X receptor, using an integrated approach, combining an in silico molecular docking technique with an optical SPR biosensor binding study. The compounds of interest were predicted and proved to target the oxysterols-binding site of human LXRα with measurable binding kinetic constants and with affinities ranging between 4.3 × 10(-7) and 4.3 × 10(-8)M. Additionally, non-cytotoxic concentration of these chemicals induced relevant changes in the LXRα gene expression levels and other target genes (SREBP-1c and LGK) in human liver hepatocellular carcinoma cell line (HepG2), as demonstrated by q-RT-PCR. Show less