Our obesity research
Garvan's obesity research is diverse and far-reaching. We're using the latest technology to translate scientific discoveries direct to the clinic. Some of our obesity focus areas include:
- prediabetes and how the microbiome affects blood sugar
- the impact of bariatric surgery on health
- the link between inflammation and obesity
- and the role of brown fat and blood sugar levels.
If you want to help make a difference, please support our research.
Key areas of investigation
Your microbiome and prediabetes
One of the major conditions travelling hand-in-hand with obesity is prediabetes – the precursor to type 2 diabetes. Prediabetes affects around 25% of Australian adults.
Prediabetes can fly under the radar for years – until the symptoms crash down like Jenga blocks. Prediabetes on its own is a risk factor for everything that diabetes can herald – cardiovascular disease, certain types of cancer, fatty liver.
But if we’re aware of prediabetes (and being overweight is one of the warning signs) there’s a lot we can do.
This is the focus of Garvan’s new clinical trial PREDICT.
“When you are already diagnosed with diabetes, it can be too late for your pancreas, because your body has been dealing with insulin resistance for many years. But during prediabetes it’s possible to prevent the development of type 2 diabetes,” says Garvan’s Dr Dorit Samocha-Bonet.
It seems like the solution is straightforward – lose weight and prevent diabetes. But many people struggle to lose weight and keep it off.
Also, weight loss does not reverse prediabetes in everybody. “On average, weight loss of about 5% of body weight, if maintained, is very beneficial for health. But we see in the clinic, and it has been documented in medical literature, that many individuals who lose a large amount of body weight and fat, do not reverse prediabetes.
“Glucose regulation remains impaired in these individuals. It’s clear that weight loss as a blanket treatment for everybody isn’t the whole story in battling the prediabetes epidemic.”
Scientists are investigating the role of the microorganisms living in our gut (our microbiome) in the current diabetes epidemic. “Our collaborators at the Weizmann Institute in Israel have shown that the sugar response to food can be predicted by the composition of the gut microorganisms and other clinical and blood parameters.”
“We also know that the drug metformin makes people more sensitive to insulin – it fights insulin resistance – but we’re still figuring out the exact mechanism. It’s emerging that metformin affects the gut microorganisms in a positive way,” says Dorit.
The genetic makeup of the billions of microorganisms in your gut could be the differentiator in how well your body processes sugar after meals and how you respond to common treatments.
“At the moment, our standard of care for a person with prediabetes is to advise a low fat, low sugar diet and try to be more active, to lose weight. But we’re looking for more precise ways to treat people.”
We hope the PREDICT study findings will lead to better tools for clinicians to guide patients on medication, diet and lifestyle choices. This will hopefully stop prediabetes from progressing to full-blown type 2 diabetes and assist those living with diabetes manage their health and improve quality of life.
- Read more about the Clinical Insulin Resistance group
Weight loss and the impact of bariatric surgery
One area of research undertaken by obesity and diabetes researchers at Garvan is understanding how weight loss improves human health and improves diabetes and related diseases. Professor Katherine Samaras, working with a team that includes scientists, cardiologists and surgeons, has been examining the impact of bariatric surgery on health.
Modest weight loss, even five kilograms, improves many health problems. It improves diabetes control, blood pressure, cholesterol and systemic inflammation. It prevents the development of diabetes in those with a high risk.
Bariatric procedures, such as gastric banding, sleeve gastrectomy and gastric bypass are proven, effective treatments for obesity, particularly where diabetes co-exists.
The team, led by Professor Samaras, recently showed that bariatric surgery reversed all cases of pre-diabetes and 70% of Type 2 diabetes within two weeks of gastric banding surgery. Data at 10 years show reversal of the majority of diabetes cases, 95% reduction in new diabetes cases, 50% reduction in new heart disease and 60% reduction of new cancers.
The evidence for the benefits of bariatric surgery is compelling, yet little is known about how the surgery and its effects on weight mediate these health improvements. Some of the research conducted at Garvan has been examining these mechanisms, particularly the way metabolism and the immune system interact.
The improvements were associated with a massive reduction in a type of white blood cell (T-lymphocyte) which act aggressively to promote systemic inflammation and tissue destruction. The reduction of these pro-inflammatory T-lymphocytes also predicted improved flexibility in the usually stiff arteries of people with diabetes, important since cardiovascular disease is the main cause of death in diabetes.
Reducing heart risk is a mainstay of diabetes care and our researchers showed that a six kilogram weight loss achieved an improvement in arterial flexibility associated with reduced heart risk. Importantly, these effects were independent of the cholesterol reduction accompanying weight loss.
It provides new information about how the hyperactive immune system is calmed by caloric restriction (fasting) and showed, for the first time, the direct link to rapid improvement in diabetes and arterial health.
Current work undertaken by Professor Samaras and collaborators includes examining adipose (fat) tissue genetic signatures that predict long term outcomes after bariatric surgery and the epigenetics of obesity – how our genes alter their expression with different environmental exposures.
- Read more about Clinical Obesity, Nutrition and Adipose Biology
Fat sends inflammation messages to the immune system
Did you know that fat sends messages to the immune system that can affect your risk of diabetes and other diseases? Researchers from Garvan and the Baker Institute are making sense of how these messages are sent, and how they might be intercepted to halt the development of disease.
Researchers believe that inflammation could be the missing link between obesity and its associated diseases. Although inflammation plays an important role in defending the body during infection, prolonged inflammation (such as in obesity) can help other diseases thrive in the body.
In obese individuals, fat pushes the immune system into ‘inflammation mode’ – but crucially, fatty tissue in leaner individuals doesn’t have the same effect.
The research team focused on fatty acids, which are known to be released in large amounts from fat in obese individuals.
“It’s these fatty acids that are driving the immune system towards inflammation in obesity,” says Professor Mark Febbraio, who led the new research.
Before the new findings, it was thought that fatty acids switched on ‘inflammation mode’ by binding directly to a particular protein (TLR4) on the surface of immune cells. The new research showed this wasn’t the case.
The researchers started their quest for answers by looked closely for definitive evidence that fatty acids were binding to, and activating, TLR4.
TLR4 ‘reprograms’ immune cells, making a series of major changes to their molecular building blocks. This reprogramming is an important part of the path to inflammation, because fatty acids can’t switch on inflammation mode without it.
There is also a big difference between the mixture of lipids in the membranes around the immune cells, and within them, before and after reprogramming.
“No one had witnessed this reprogramming before,” says Prof Febbraio. “It’s a real eye-opener, and it makes it clear that there are steps on the path to inflammation that we had no idea about before.
The findings open up several new approaches to halting obesity-induced inflammation. In particular, Prof Febbraio says, targeting the changes to membranes is a promising approach for therapeutic discovery.
The research was undertaken by the Garvan Institute and the Baker Heart and Diabetes Institute.
- Read more about Cellular and Molecular Metabolism
Brown fat and blood sugar levels
Garvan scientists have shown that brown fat – a type of fat that burns energy to keep us warm – can also help keep blood sugar steady in adults.
We measured brown fat activity and blood glucose continuously in real time in study participants, and found that individuals with more brown fat had smaller fluctuations in blood sugar.
The incidence of type 2 diabetes, which is characterised by high blood sugar, is reaching epidemic proportions worldwide. There is a need for new insights into how blood sugar levels can be controlled, beyond mechanisms actioned by currently available therapies.
Unlike white fat, which primarily stores energy, brown fat burns energy – often in remarkably large amounts. Sitting just above the collarbone and in the neck, brown fat acts like a heat generator, helping to keep us warm by burning sugar and fat.
Associate Professor Jerry Greenfield, of Garvan’s Diabetes and Metabolism Division, has long been interested in whether brown fat might have a role beyond keeping us cosy.
“Previously, we showed that individuals with large brown fat stores tend to be lean and have lower blood glucose – and now, we’ve uncovered a potential link between brown fat activity and blood glucose variations”.
The research team studied a group of 15 healthy adults over 12 hours. They found that blood glucose levels and heat production by brown fat were closely related, tracking together over time.
Importantly, participants who had larger deposits of brown fat had less fluctuation in blood glucose – and blood glucose fell after each peak of brown fat activity surge.
In contrast, brown fat activity rose only in response to an increase in blood glucose among those with less brown fat, and interestingly, their glucose fluctuations were greater. Notably, individuals with no detectable brown fat had the widest fluctuations in blood glucose.
It looks like the more brown fat one has, the more influence it has on blood glucose.
Our findings indicate that brown fat might act as a ‘glucose buffer’, lessening the variation in blood glucose and potentially diminishing metabolic stresses that could increase the risk of diabetes.
The researchers also observed that brown fat activity rose at dawn, around the time volunteers were waking from sleep. We speculate that this early morning temperature boost may have an evolutionary origin, generating heat and preparing our ancestors for hunting and gathering in the cold as the day begins.
Brown fat-based therapies are potentially promising in the fight against diabetes in the future, but also urges caution.
“The study brings brown fat into the frame for developing diabetes therapies. If we can pinpoint what switches brown fat’s activity on and off during the day, we may identify new targets in drug design.
“Brown fat is interesting and promising – but it is not the solution to finding a cure for diabetes, at least not now. A balanced diet and regular exercise are the cornerstones of healthy metabolism and should not be forgotten.”
- Read more about Clinical Diabetes, Appetite and Metabolism