Tomohiro TanakaDr. Japan

• Brain Remodeling of Appetite Centers in Obesity - Results from Murine Omics Studies and Human Brain Imaging
  Tomohiro TanakaJapan Speaker Brain Remodeling of Appetite Centers in Obesity - Results from Murine Omics Studies and Human Brain ImagingBody weight is regulated by functional interplay between multiple organs, among which the hypothalamus plays a critical role through its modulatory functions on energy intake and expenditure. In early 1900s, professors Joseph Babinski and Alfred Frolich reported a case of acquired hypothalamic obesity, whose obesity was secondary to hypothalamic damage by brain tumor. The case provides the first evidence that the hypothalamus plays a key role in the maintenance of body weight in humans. In the 1970s and 1980s, experimental injury or electrical stimulation of the hypothalamic nuclei in rodents further led to an elucidation of its vital role in body weight regulation. Mechanistic insight has been addressed when the discovery of leptin followed by an elucidation of anorexigenic effect of GLP-1 has cast limelight on the endocrinologic aspect of body weight regulation. In fact, more than a dozen genetic forms of obesity has been reported, each of which is caused by mutations of a single gene with indispensable functions within leptin-hypothalamus axis. However, in routine clinical practice, tumors or genetic abnormalities in the hypothalamus are rarely observed in patients with obesity disease. The question, then, is whether the hypothalamus is functioning normally in such patients with primary obesity disease? In 2012, professor Joshua Thaler and colleagues reported that mice fed a high-fat diet exhibit early activation and proliferation of microglia and astrocytes within the hypothalamus - histologic changes suggestive of "hypothalamic inflammation". Subsequent pharmacologic and knockout mouse studies have demonstrated that this hypothalamic inflammation is not merely a result but a critical cause of obesity. We have studied the molecular landscape and its alterations during the development or the improvement of the obesity disease. Methodologically, our research involves transcriptomic and lipidomic analyses of hypothalamic nuclei in mice, with the aim of elucidating the molecular basis of hypothalamic remodeling observed in obese animal models. We have identified obesity-induced biochemical changes in the hypothalamus, such as inflammation-related transcriptome and region-specific accumulation of arachidonic acid esters. More clinically, we are investigating a potential reverse remodeling of the hypothalamus during weight loss in mouse models. Of note, in human subjects with obesity disease, reversible hypothalamic inflammation has been demonstrated using T2 relaxation time measurements in MRI studies. As such, hypothalamic inflammation, a common feature of hypothalamic pathology in rodents and humans, is attracting more attention as a focus of obesity research. In this session, I would like to discuss more of the status quo and future perspectives of the neuropathologic basis of the obesity disease.
• Obesity Management: What's New?
  Alice KongHong Kong, China Speaker Obesity: What Clinicians Should KnowRapid changes in technology, human behavior and lifestyle over the past few decades have resulted in a dramatic increase in the prevalence of obesity worldwide. Besides social stigmata and psychological consequences, obesity is associated with escalated risks of type 2 diabetes, coined the term "Diabesity", hypertension, dyslipidemia, sleep apnoea, metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), polycystic ovarian syndrome, cancers, cardiovascular diseases and increased mortality. Body mass index (BMI) is a commonly adopted tool to identify people with obesity. Clinicians should note that the cutoff points of BMI for clinical actions are different between people with obesity from the East and the West, as well as the limitations of BMI in diagnosing obesity. Recently, the Lancet Diabetes and Endocrinology Commission proposed a new definition of obesity which differentiates excess adiposity with obesity-related illness (clinical obesity) from those without obesity-related diseases (pre-clinical obesity). Also, people with clinical obesity have many unmet needs requiring personalized treatment regimens, intensive counselling and emotional support. The 5 A's framework including Ask, Assess, Advise, Agree and Assist, provide a patient-centred approach to promote lasting behavioral change in obesity management. In addition to lifestyle modifications and behavioral changes, pharmacological agents for weight reduction, bariatric and metabolic surgeries are therapeutic options requiring careful selections for the appropriate patients with adequate counselling of the risks and benefits. Through case sharing approach, the use of weight reducing drugs and surgical strategies for people with preclinical and clinical obesity will be discussed in this session. Acknowledgement: The work described in this lecture was partially supported by funding from Health and Medical Research Fund (HMRF), Food and Health Bureau, Hong Kong SAR, China (Reference number:21223391), Matching Grant from Research Grants Council (reference number: 8601556), and Area of Excellence Scheme, Research Grants Council, Hong Kong SAR, China (Reference number: AoE/M-401/24-R). Obesity Management: What's New?Obesity is a global health hazard with rising prevalence in most parts of the world. Weight reduction by lifestyle modification remains the cornerstone in the prevention and treatment of obesity. However, weight management by lifestyle therapy alone is difficult to sustain in many obese individuals with rebound of body weight being observed as a common phenomenon. Given the invasiveness of bariatric and metabolic surgeries which are not accepted by many people with obesity, the use of pharmacological agents in weight management is increasingly popular. In 2025, the Lancet Diabetes and Endocrinology Commission proposed a new definition of obesity which differentiates excess adiposity with obesity-related illness (clinical obesity) from those without obesity-related diseases (pre-clinical obesity). Among the various obesity complications, diabetes is well recognized to be closely related to obesity, with the term 'Diabesity' coined to show the strong link between these two important modifiable risk factors of cardiovascular disease and premature death. In recent decades, many new generation anti-diabetic drugs are developed and found to have weight reducing properties. Looking ahead, more new drugs are in the pipeline of clinical trials, and the results may eventually change the landscape of obesity management. Acknowledgement: The work described in this lecture was partially supported by funding from Health and Medical Research Fund (HMRF), Food and Health Bureau, Hong Kong SAR, China (Reference number:21223391), Matching Grant from Research Grants Council (reference number: 8601556), and Area of Excellence Scheme, Research Grants Council, Hong Kong SAR, China (Reference number: AoE/M-401/24-R).
• The Hidden Barrier: Understanding and Overcoming Weight Bias
  Hai-Hua ChuangTaiwan Speaker The Hidden Barrier: Understanding and Overcoming Weight Bias