Lipid Metabolism In The Aromatase Knock-out Mouse (ArKO)
Funder
National Health and Medical Research Council
Funding Amount
$408,055.00
Summary
Studies of humans with natural mutations in aromatase, the enzyme responsible for oestrogen biosynthesis, have revealed a number of unexpected roles for oestrogens in both males and females. These discoveries even challenge the definitions of oestrogens and androgens as we now know them. We have created a mouse model of oestrogen insufficiency by targetted disruption of the aromatase gene. These mice display a number of age dependent phenotypes including both male and female infertility, undermi ....Studies of humans with natural mutations in aromatase, the enzyme responsible for oestrogen biosynthesis, have revealed a number of unexpected roles for oestrogens in both males and females. These discoveries even challenge the definitions of oestrogens and androgens as we now know them. We have created a mouse model of oestrogen insufficiency by targetted disruption of the aromatase gene. These mice display a number of age dependent phenotypes including both male and female infertility, undermineralisation of the bones, intra-abdominal obesity, hypercholesterolaemia and insulin resistance. We are addressing the mechanisms of all of those phenotypes but in the present application we focus on the abnormalities in lipid metabolism. Thus we will seek to understand the increase in adiposity by examining the role of oestrogen in lipid synthesis, oxidation and breakdown in adipose tissue from intra-abdominal sites. We will also examine the role that oestrogen plays in cholesterol uptake, synthesis and catabolism by the liver as well as fatty acid synthesis and oxidation by the liver. These studies will be correlated with whole body parameters such as feeding behaviour, physical activity, energy expenditure, glucose and fat oxidation rates. We will also examine the effect of feeding a high cholesterol or a high fat diet on lipid metabolism in the oestrogen deficient animals, and we will determine the effect of oestradiol and isoflavone replacement on the phenotype. In this way we aim to reach a better understanding of the multiplicity of roles that oestrogens play in the regulation of lipid and cholesterol metabolism in both males and females. The results of such studies will be the development of better strategies to deal with pathologies resulting from disturbances in cholesterol and lipid metabolism.Read moreRead less
Transcriptome Landscape Of Brown/beige Adipogenesis In Humans
Funder
National Health and Medical Research Council
Funding Amount
$393,369.00
Summary
There are three kinds of fat in the body: white, brown and beige. While excess white fat results in obesity, brown fat is associated with leanness and lowers blood glucose levels. Recent animal experiments show that under certain conditions, white fat can be transformed into beige fat, leading to benefits such as weight loss. The current project grant involves examination of human fat cells grown in the laboratory and investigation on the genetics of brown and beige fat.
The Interaction Between Sexually Transmissible Infections And Human Immunodeficiency Virus Infection In Homosexual Men
Funder
National Health and Medical Research Council
Funding Amount
$635,931.00
Summary
This project examines the inter-relationship between HIV infection and sexually transmitted infections (STIs) in homosexual men. The overall goal of the projet is to inform the development of STI prevention and treatment strategies which may be important in reducing HIV incidence in this population. Homosexual men comprise over 80% of people diagnosed with HIV infecton in Australia, and in many developed nations are one of the largest groups affected by HIV. Rates of other STIs are also increase ....This project examines the inter-relationship between HIV infection and sexually transmitted infections (STIs) in homosexual men. The overall goal of the projet is to inform the development of STI prevention and treatment strategies which may be important in reducing HIV incidence in this population. Homosexual men comprise over 80% of people diagnosed with HIV infecton in Australia, and in many developed nations are one of the largest groups affected by HIV. Rates of other STIs are also increased in homosexual men. Currently, HIV rates are increasing in Australia and in many developed countries. We are in need of new and effective methods of HIV prevention. Data in heterosexuals suggest that where STIs are common, the early detection and treatment of these infections may help reduce HIV incidence. There are few data on this relationship in homosexual men. We propose to utilise an existing Sydney cohort of homosexual men to collect data on biologic tests for STIs, history of recent diagnosis of STIs, and symptoms, to allow a comprehensive description of the epidemiology of STIs and their overlap with HIV. The quality of data on the interaction between HIV and STIs in this cohort will be superior to any previously collected in homosexual men, as it will include data on self-reported doctor diagnosed illness, state of the art biologic testing, and symptom data, for the full spectrum of important STIs. The results of this study will be helpful in determining strategies for HIV and STI screening, education and control in the population which comprises the great majority of cases of HIV infection in Australia, and one of the largest risk groups for HIV infection in the developed world. Screening coupled with treatment of asymptomatic STIs may be an effective new approach to HIV prevention in this population.Read moreRead less
Transgenerational Effects Of Male Obesity - Mechanisms And Interventions
Funder
National Health and Medical Research Council
Funding Amount
$829,143.00
Summary
Childhood obesity is associated with obesity in either parent, and obese children tend to become obese adults, forming an intergenerational cycle that promotes obesity. We have identified paternal obesity as an important novel target for intervention to stop the progression of the obesity epidemic. This project investigates supplementation of obese fathers with folate to prevent the adverse impact of paternal obesity on subsequent generations.
Chemerin, A Novel Therapeutic Target For Modulation Of Adipose Tissue Mass
Funder
National Health and Medical Research Council
Funding Amount
$535,621.00
Summary
Obesity is a significant public health issue due to its increasing prevalence and association with other diseases including cardiovascular disease. Efforts to pharmacologically prevent and treat obesity are impaired by an incomplete understanding of the genes and metabolic processes involved. This project will use cell and animal models to examine the processes that occur during the expansion of fat tissue which will broaden our understanding of obesity and assist in identifying new therapies.