Sex-Dependent Role of Adipose Tissue HDAC9 in Diet-Induced Obesity and Metabolic Dysfunction.

Obesity is a major risk factor for both metabolic and cardiovascular disease. We reported that, in obese male mice, histone deacetylase 9 (HDAC9) is upregulated in adipose tissues, and global deletion of HDAC9 protected against high fat diet (HFD)-induced obesity and metabolic disease. Here, we investigated the impact of adipocyte-specific HDAC9 gene deletion on diet-induced obesity in male and female mice. The HDAC9 gene expression was increased in adipose tissues of obese male and female mice and HDAC9 expression correlated positively with body mass index in humans. Interestingly, female, but not male, adipocyte-specific HDAC9 KO mice on HFD exhibited reduced body weight and visceral adipose tissue mass, adipocyte hypertrophy, and improved insulin sensitivity, glucose tolerance and adipogenic differentiation gene expression. Furthermore, adipocyte-specific HDAC9 gene deletion in female mice improved metabolic health as assessed by whole body energy expenditure, oxygen consumption, and adaptive thermogenesis. Mechanistically, compared to female mice, HFD-fed male mice exhibited preferential HDAC9 expression in the stromovascular fraction, which may have offset the impact of adipocyte-specific HDAC9 gene deletion in male mice. These results suggest that HDAC9 expressed in adipocytes is detrimental to obesity in female mice and provides novel evidence of sex-related differences in HDAC9 cellular expression and contribution to obesity-related metabolic disease.

Differential Toxicities of Nickel Salts to the Nematode Caenorhabditis elegans.

This study focused on assessing whether nickel (Ni) toxicity to the nematode Caenorhabditis elegans was affected by the molecular structure of the Ni salt used. Nematodes were exposed to seven Ni salts [Ni sulfate hexahydrate (NiSO4·6H2O), Ni chloride hexahydrate (NiCl2·6H2O), Ni acetate tetrahydrate (Ni(OCOCH3)2·4H2O), Ni nitrate hexahydrate (N2NiO6·6H2O), anhydrous Ni iodide (NiI2), Ni sulfamate hydrate (Ni(SO3NH2)2·H2O), and Ni fluoride tetrahydrate (NiF2·4H2O)] in an aquatic medium for 24 h, and lethality curves were generated and analyzed. Ni fluoride, Ni iodide, and Ni chloride were most toxic to C. elegans, followed by Ni nitrate, Ni sulfamate, Ni acetate, and Ni sulfate. The LC50 values of the halogen-containing salts were statistically different from the corresponding value of the least toxic salt, Ni sulfate. This finding is consistent with the expected high bioavailability of free Ni ions in halide solutions. We recommend that the halide salts be used in future Ni testing involving aquatic invertebrates.