American association of clinical endocrinologists and american college of endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity.

THP-1 cell line: an in vitro cell model for immune modulation approach.

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.

The genetic architecture of type 2 diabetes

Zinc is involved in a variety of biological processes, as a structural, catalytic, and intracellular and intercellular signaling component. Thus zinc homeostasis is tightly controlled at the whole ...

The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism.

Mammalian zinc transport, trafficking, and signals.

Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease in both adults and children worldwide. As a disease spectrum, NAFLD may progress from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. An estimated 20-35% of the general population has steatosis, 10% of whom will develop the more progressive non-alcoholic steatohepatitis associated with markedly increased risk of cardiovascular- and liver-related mortality. Development of NAFLD is strongly linked to components of the metabolic syndrome including obesity, insulin resistance, dyslipidaemia and type 2 diabetes. The recognition that NAFLD is an independent risk factor for CVD is a major public health concern. There is a great need for a sensitive non-invasive test for the early detection and assessment of the stage of NAFLD that could also be used to monitor response to treatment. The cellular and molecular aetiology of NAFLD is multi-factorial; genetic polymorphisms influencing NAFLD have been identified and nutrition is a modifiable environmental factor influencing NAFLD progression. Weight loss through diet and exercise is the primary recommendation in the clinical management of NAFLD. The application of systems biology to the identification of NAFLD biomarkers and factors involved in NAFLD progression is an area of promising research.

/pdf/non-alcoholic-fatty-liver-disease-the-hepatic-consequence-of-149i7bkwg3.pdf

Non-alcoholic fatty liver disease: the hepatic consequence of obesity and the metabolic syndrome

Among the micronutrients required by humans, zinc has particularly divergent modes of action. cDNA microarray and quantitative PCR technologies were used to investigate the zinc responsiveness of known genes that influence zinc homeostasis and to identify, through global screening, genes that may relate to phenotypic outcomes of altered dietary zinc intake. Human monocytic/macrophage THP-1 cells were either acutely zinc depleted, using a cell-permeable zinc-specific chelator, or were supplemented with zinc to alter intracellular zinc concentrations. Initially, genes associated with zinc homeostasis were evaluated by quantitative PCR to establish ranges for fold changes in transcript abundance that might be expected with global screening. Zinc transporter-1 and zinc transporter-7 expression increased when cellular zinc increased, whereas Zip-2 expression, the most zinc-responsive gene examined, was markedly increased by zinc depletion. Microarrays composed of approximately 22,000 elements were used to identify those genes responsive to either zinc depletion, zinc supplementation, or both conditions. Hierarchal clustering and ANOVA revealed that approximately 5% or 1,045 genes were zinc responsive. Further sorting based on this pattern of the zinc responsiveness of these genes into seven groups revealed that 104 genes were linearly zinc responsive in a positive mode (i.e., increased expression as cellular zinc increases) and 86 genes that were linearly zinc responsive in a negative mode (i.e., decreased expression as cellular zinc increases). Expression of some genes was responsive to only zinc depletion or supplementation. Categorization by function revealed numerous genes needed for host defense were among those identified as zinc responsive, including cytokine receptors and genes associated with amplification of the Th1 immune response.

https://www.pnas.org/content/pnas/100/12/6952.full.pdf

A global view of the selectivity of zinc deprivation and excess on genes expressed in human THP-1 mononuclear cells

Differential mRNA display and cDNA array analysis have identified zinc-regulated genes in small intestine, thymus and monocytes. The vast majority of the transcriptome is not influenced by dietary zinc intake, high or low. Of the genes that are zinc regulated, most are involved in signal transduction (particularly influencing the immune response), responses to stress and redox, growth and energy utilization. Among the genes identified are uroguanylin (UG), cholecystokinin, lymphocyte-specific protein tyrosine kinase (LCK), T-cell cytokine receptor, heat shock proteins and the DNA damage repair and recombination protein-23B. Zinc transporters (ZnT) help regulate the supply of this micronutrient to maintain cellular functions. Expression of ZnT-1 and -2 is regulated by dietary zinc in many organs including small intestine and kidney. ZnT-4 is ubiquitously expressed but is refractory to zinc intake. Expression of ZnT-1, -2 and -4 changes markedly during gestation and lactation from highly abundant to undetectable. Each ZnT has an endosomal-like appearance in the tissues examined. Upregulation of ZnT-1 and ZnT-2 by dietary zinc strongly implicates these transporters in zinc acquisition and/or storage for subsequent systemic needs. THP-1 cells were used as a model to examine the response of human cells to changes in zinc status. Based on mRNA quantities, Zip1 and ZnT-5 were the most highly expressed. Zinc depletion of these cells decreased expression of all transporters except Zip2, where expression increased markedly. Collectively, these findings provide a genomic footprint upon which to address the biological and clinical significance of zinc and new avenues for status assessment.

Regulation of Zinc Metabolism and Genomic Outcomes

Background Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, with prevalence above 30% in many adult populations. Strongly associated with obesity, weight loss through diet and physical activity is the mainstay of its management. Weight loss can be difficult to achieve and maintain however, and uncertainty exists as to which lifestyle changes are most effective. Objective The aim of this work was to systematically evaluate randomised controlled trials assessing diet, exercise or combination interventions aimed at reducing steatosis or markers of NAFLD activity. Design Medline, Scopus and Cochrane databases were searched from 1 January 1980 through to 31 July 2016, for intervention trials assessing the effects of diet, weight loss, exercise or any combination thereof, on NAFLD disease markers in human adults. Risk of publication bias and study quality was assessed using the American Dietetic Association Quality Criteria Checklist. Results From a total of...

https://bmjopengastro.bmj.com/content/bmjgast/4/1/e000139.full.pdf

Efficacy of dietary and physical activity intervention in non-alcoholic fatty liver disease: a systematic review

Objectives: To comprehensively survey the sugar and
nutrient contents of yogurt products available in UK
supermarkets, in particular those marketed to children.
Design: A cross-sectional survey of yogurt products
available in the UK’s supermarkets in November 2016.
Methods: Data were collected from five major online
UK supermarkets and a process flow strategy was used
to place yogurts into eight categories: children’s, dairy
alternatives, dessert, drinks, fruit, flavoured, natural/Greek
style and organic. A comprehensive database of product
information for 921 unique products was created and
analysed.
Results: The total sugar, fat, protein, calcium and energy
contents were highly variable across categories, and
the ranges were extremely broad. Although lower than
the dessert category, the medians (range) of the total
sugar content of children’s (10.8 g/100 g (4.8–14.5)),
fruit (11.9 g/100 g (4.6–21.3)), flavoured (12.0 g/100 g
(0.1–18.8)) and organic (13.1 g/100 g (3.8–16.9)) yogurt
products were all well above 10 g/100 g, and represented
>45% of total energy. Only two out of 101 children’s
yogurt and fromage frais products surveyed qualified
as low sugar (≤5 g/100 g). Natural/Greek yogurts had
dramatically lower sugar contents (5.0 g/100 g (1.6, 9.5),
largely lactose) than all other categories. While low-fat
(<3 g/100 g) products had less sugar and energy than
higher fat yogurts, nonetheless 55% (285 of 518 low-fat
yogurts) contained between 10 and 20 g sugar/100 g.
Within the children’s category, fromage frais had higher
protein (5.3 g/100 g (3.3, 8.6) vs 3.2 (2.8, 7.1); p<0.0001)
and calcium contents (150 mg/100 g (90, 240) vs
130.5 mg/100 g (114, 258); p=0.0015) than yogurts.
Conclusions: While there is good evidence that yogurt
can be beneficial to health, products on the market vary
widely in total sugars. Fewer than 9%, and only 2% of
the children’s, products surveyed were low enough in
sugar to earn ‘green’ in UK front of the pack labelling.
Reformulation for the reduction of free sugars in yogurts is
warranted.

https://bmjopen.bmj.com/content/bmjopen/8/8/e021387.full.pdf

J. Bernadette Moore

Papers

Non-alcoholic fatty liver disease: the hepatic consequence of obesity and the metabolic syndrome

A global view of the selectivity of zinc deprivation and excess on genes expressed in human THP-1 mononuclear cells

Regulation of Zinc Metabolism and Genomic Outcomes

Efficacy of dietary and physical activity intervention in non-alcoholic fatty liver disease: a systematic review

Evaluation of the nutrient content of yogurts: a comprehensive survey of yogurt products in the major UK supermarkets