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2022 JUL 16 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Data detailed on hypoalphalipoproteinemias have been presented. According to news originating from [...]

2022 FEB 12 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- Data detailed on Genetics - Human Genetics have been presented. According to [...]

During chronic caloric excess, adipose tissue expands primarily by enlargement of individual adipocytes, which become stressed with lipid overloading, thereby contributing to obesity-related disease. Although adipose tissue contains numerous preadipocytes, differentiation into functionally competent adipocytes is insufficient to accommodate the chronic caloric excess and prevent adipocyte overloading. We report for the first time that a chronic high-fat diet (HFD) impairs adipogenic differentiation, leading to accumulation of inefficiently differentiated adipocytes with blunted expression of adipogenic differentiation-specific genes. Preadipocytes from these mice likewise exhibit impaired adipogenic differentiation, and this phenotype persists during in vitro cell culture. HFD-induced impaired adipogenic differentiation is associated with elevated expression of histone deacetylase 9 (HDAC9), an endogenous negative regulator of adipogenic differentiation. Genetic ablation of HDAC9 improves adipogenic differentiation and systemic metabolic state during an HFD, resulting in diminished weight gain, improved glucose tolerance and insulin sensitivity, and reduced hepatosteatosis. Moreover, compared with wild-type mice, HDAC9 knockout mice exhibit upregulated expression of beige adipocyte marker genes, particularly during an HFD, in association with increased energy expenditure and adaptive thermogenesis. These results suggest that targeting HDAC9 may be an effective strategy for combating obesity-related metabolic disease. Diabetes 2014;63:176-187 | DOI: 10.2337/db13-1148, Adipose tissue plays a vital homeostatic role in storing excess calories as triglyceride lipid within adipocytes. Adipocytes also function as endocrine cells, secreting hormones and biologically active molecules that regulate [...]

The major diabetes quantitative trait locus (Niddm1), which segregates in crosses between GK rats affected with spontaneous type 2-like diabetes and normoglycemic F344 rats, encodes at least two different diabetes susceptibility genes. Congenic strains for the two subloci (Niddm1f and Niddm1i) have been generated by transfer of GK alleles onto the genome of F344 rats. Whereas the Niddm1f phenotype implicated insulin resistance, the Niddm1i phenotype displayed diabetes related to insulin deficiency. Individual islets from 16-week-old congenic rats were characterized for insulin release and oxygen tension (P[O.sub.2]). In the presence of 3 mmol/l glucose, insulin release from Niddm1f and Niddm1i islets was ~5 pmol x [g.sup.-1] x [s.sup.-1] and p[O.sub.2] was 120 mmHg. Similar recordings were obtained from GK and F344 islets. When glucose was raised to 11 mmol/l, insulin release increased significantly in Niddm1f and F344 islets but was essentially unchanged in islets from GK and Niddm1i. The high glucose concentration lowered p[O.sub.2] to the same extent in islets from all strains. Addition of 1 mmol/l tolbutamide to the perifusion medium further increased pulsatile insulin release threefold in all islets. The pulse frequency was ~0.4 [min.sup.-1] x α-Ketoisocaproate (11 mmol/l) alone increased pulsatile insulin release eightfold in islets from Niddm1f, Niddm1i, and control F344 rats but had no effect on insulin release from GK islets. These secretory patterns in response to α-ketoisocaproate were paralleled by reduction of p[O.sub.2] in Niddm1f, Niddm1i, and control F344 islets and no change of p[O.sub.2] in GK islets. The results demonstrate that Niddm1i carries alleles of gene(s) that reduce glucose-induced insulin release and that are amenable to molecular identification by genetic fine mapping., Type 2 diabetes is a multifactorial disease that is influenced by environmental and genetic factors (1-3). The disease is a heterogeneous metabolic disorder characterized by impairment of insulin secretion from [...]

Scientists discuss in 'Design and validation of a metabolic disorder resequencing microarray (BRUM1)' new findings in metabolic disorders. 'The molecular genetic diagnosis of inherited metabolic disorders is challenging. The diseases [...]

Phenylketonuria (PKU) is a genetic disorder characterized by the inability to convert the amino acid phenylalanine to tyrosine. If untreated, the patient with PKU develops brain damage and mental retardation. Screening for PKU at birth is required in some states. The outcome of infants born to mothers with PKU has been studied, but there is limited information about the outcome of infants born to fathers with PKU. Hence, the outcome of children of fathers with PKU and the ability of men with PKU to produce children were assessed. In addition, the children of fathers with PKU were compared with those of mothers with PKU to determine whether genetic as well as metabolic factors are responsible for several abnormalities observed in children of mothers with PKU. Few men with PKU were followed-up to 18 years and older. A review of previous reports of males with PKU showed that eight fathers with PKU fathered 26 children, including 10 with PKU and nine with an intelligence quotient of less than 80. In contrast to children of mothers with PKU, children of fathers with PKU did not have physical or mental defects other than PKU. Increases in blood levels of phenylalanine were associated with decreases in sperm count and semen volumes. Men with PKU are capable of having children but may have a limited ability to reproduce. Evidence suggests that genetic inheritance of PKU does not increase the incidence of PKU among offspring or cause other damage. (Consumer Summary produced by Reliance Medical Information, Inc.)

The deoxyribonucleic acid (DNA) binding profiles of upstream stimulatory factors 1 and 2 (USF1 and USF2) and acetylated histone H3 (H3ac) in a liver cell line were mapped for the whole human genome. Results reveal new human promoter architecture as well as genes with a bidirectional conformation and a set of candidate genes for common metabolism disorders.

Primary Systemic Carnitine Deficiency is Caused by Mutations in a Gene Encoding Sodium-Ion-Dependent Carnitine Transporter Nezu JI, Tamai I, Oku A, et al. Nature Genet. 1999;21:90-94. Summary: Primary systemic carnitine [...]