Cardiometabolic Changes in Sirtuin1-Heterozygous Mice on High-Fat Diet and Melatonin Supplementation.

A hypercaloric fatty diet predisposes an individual to metabolic syndrome and cardiovascular complications. Sirtuin1 (SIRT1) belongs to the class III histone deacetylase family and sustains anabolism, mitochondrial biogenesis, and fat distribution. Epididymal white adipose tissue (eWAT) is involved in inflammation, whilst interscapular brown adipose tissue (iBAT) drives metabolism in obese rodents. Melatonin, a pineal indoleamine, acting as a SIRT1 modulator, may alleviate cardiometabolic damage. In the present study, we morphologically characterized the heart, eWAT, and iBAT in male heterozygous SIRT1+/- mice (HET mice) on a high-fat diet (60%E lard) versus a standard rodent diet (8.5% E fat) and drinking melatonin (10 mg/kg) for 16 weeks. Wild-type (WT) male C57Bl6/J mice were similarly fed for comparison. Cardiomyocyte fibrosis and endoplasmic reticulum (ER) stress response worsened in HET mice on a high-fat diet vs. other groups. Lipid peroxidation, ER, and mitochondrial stress were assessed by 4 hydroxy-2-nonenal (4HNE), glucose-regulated protein78 (GRP78), CCAA/enhancer-binding protein homologous protein (CHOP), heat shock protein 60 (HSP60), and mitofusin2 immunostainings. Ultrastructural analysis indicated the prevalence of atypical inter-myofibrillar mitochondria with short, misaligned cristae in HET mice on a lard diet despite melatonin supplementation. Abnormal eWAT adipocytes, crown-like inflammatory structures, tumor necrosis factor alpha (TNFα), and iBAT whitening characterized HET mice on a hypercaloric fatty diet and were maintained after melatonin supply. All these data suggest that melatonin's mechanism of action is strictly linked to full SIRT1 expression, which is required for the exhibition of effective antioxidant and anti-inflammatory properties.

"Aged" autopsy gallstones simulating dry bone context: A morphological, histological and SEM-EDS analysis.

OBJECTIVE: The aim of this paper is to provide information on the morphology and composition of gallstones based on clinical samples in order to assist paleopathologists and bioarchaeologists in recognizing their presence in archaeological contexts. MATERIALS AND METHODS: 270 gallstones were extracted and macerated from autopsies conducted at the Istituto di Medicina Legale in Milan (Italy) in order to simulate a dry bone recovered from archaeological contexts. Morphological, histological, and elemental variation was documented. RESULTS: Gallstones vary in size, shape, color and texture. The cross-sectional surface correlates with chemical composition and is a valuable tool for classification into subcategories of stones. Histological analysis can confirm the classification. Elemental analysis yielded a higher frequency of carbon, calcium and phosphorus. CONCLUSIONS: Although identification of gallstones in archaeological contexts can be challenging, familiarity with morphological, histological, and elemental variation can assist researchers in the field and laboratory. SIGNIFICANCE: Identifying gallstones in archaeological populations will assist researchers in estimating their frequency in the past and the environmental, cultural, and biological conditions leading to their presence. LIMITATIONS: Small sample size derived from a modern and limited autopsy population may minimize the types and degree of variation present in the past. Effects of climate, soil, and taphonomy were not evaluated. SUGGESTIONS FOR FURTHER RESEARCH: Examination of larger samples derived from diverse populations may reveal greater variation or more diagnostic aspects of stones.