High-Fat Diet: A Paradoxical Factor in the Setting of Type 1 Diabetes

Type 1 diabetes (T1D) stems from the autoimmune attack on insulin-producing pancreatic islet β cells. Progression of T1D is fundamentally dictated by genetic predisposition and modified by environmental and dietary factors. Although patients with T1D are typically characterized by weight loss, overweight and obesity have become more prevalent in recent years. This phenomenon is related to the intake of fat beyond the recommended limit, and a high-fat diet (HFD) is speculated to elevate the risk of T1D along with the development of diabetic complications. By contrast, results of studies in animal models are somehow contradictory: some suggest an HFD has a detrimental effect, others support a protective role. Herein these findings are summarized, and contradictory findings are termed the "fat paradox." The paradoxical roles of an HFD in the T1D setting are discusses, and the potential mechanistic explanations are delved into from the perspectives of immune regulation, β-cell fitness, gut microbiota remodeling, and HFD composition. The opposite effects of saturated fatty acids (SFAs) and unsaturated fatty acids, especially n-3 polyunsaturated fatty acids (PUFAs), are particularly emphasized. Specifically, SFAs instigate pro-inflammatory responses and reduce the abundance of bacterial that produced short-chain fatty acids (SCFAs), whereas n-3 PUFAs have anti-inflammatory properties and facilitate the enrichment of SCFA-producing bacteria. Altogether, the multifaceted roles of fat uptake under T1D setting indicate a potential dietary intervention strategy with tailored fat types and optimized intake levels.