When brown fat cells start sending the wrong signals, the body’s energy balance can shift in unexpected ways, which is bad news for people living with obesity and type 2 diabetes.
Dr Khanyisani Ziqubu, a PhD student from the North-West University (NWU), set out to investigate how brown fat behaves in obesity and whether plant-based compounds might help steer it back on track.
Dr Ziqubu recently graduated with a PhD in Biochemistry, with seven publications that came from his PhD. He led the study, which focused on brown adipose tissue (BAT), a special kind of fat. BAT is distinct from the obesogenic white adipose tissue (WAT) – known to store excess energy as fat.
BAT burns fat and produces signalling molecules known as batokines, which act like messengers for inter-organ communication and help to keep the body’s metabolic system running smoothly. But in people living with obesity and type 2 diabetes, these signals appear to go off.
“I wanted to understand how batokines change during obesity and if natural compounds and flavanoids found in plants, can help regulate their production,” says Dr Ziqubu.
Brown fat turns white as obesity progresses
Collaborating with scientists from, South African Medical Research Council and the University of KwaZulu Natal, Dr Ziqubu conducted both animal and cell-based experiments. He studied obese and diabetic mice of different ages, tracking body weight, blood sugar and insulin resistance over time. They also looked at the architecture of brown fat in these mice.
The results showed that as obesity progressed, brown fat began to resemble white fat, which is mainly for storing energy. This “whitening” of brown fat was linked to increased inflammation and reduced activity of thermogenic genes, which are usually responsible for burning energy.
In the laboratory, Dr Ziqubu used a brown fat cell line and exposed it to palmitic acid, a fatty acid common in high-fat diets. The cells began to store large fat droplets, mimicking the same kind of changes seen in WAT from the obese mice.
“I observed a progressive loss of the original function of brown fat and becoming more inflammatory with abnormal release of its signalling molecules,” says Dr Ziqubu.
Bringing plant flavonoids into the picture
Dr Ziqubu also measured the expression of several genes linked to glucose regulation, fat metabolism, nerve growth and inflammation. These included Glut-4, AdipoQ, and VegfA, genes known to play key roles in how the body handles sugar, fat and blood vessels.
In a published review by Dr Ziqubu and team, literature suggests that plant-based compounds may help normalise batokine activity and improve metabolism.
“There is growing interest in how natural flavonoids might support the regulation of brown fat function,” says Prof Sithandiwe Mazibuko-Mbeje who supervised the study. “Our findings give a possible direction for future research on flavonoid-based therapies.”
As obesity and type 2 diabetes continue to rise in South Africa and globally, understanding how tissues like brown fat contribute to disease progression could help identify new therapeutic strategies. The NWU-led team believes their model may be a useful tool in that search.
“We’re just beginning to uncover the full role of batokines,” says Dr Ziqubu. “But this work adds to the growing body of evidence that they are key players in metabolic health.”
This study was presented in prestigious international conferences, including Biomolecular Horizons 2024 Congress in Australia, 21st International Congress of Endocrinology in the United Arab Emirates, and the Mitochondrial Physiology - from Organelle to Organism Congress in Denmark. For this work, Dr Ziqubu became one of the outstanding PhD candidates globally to be awarded Young Scientific Program 2024 in Australia.
Dr Khanyisani Ziqubu and his PhD promoter Prof Prof Sithandiwe Mazibuko-Mbeje.
