How do adipose tissue macrophages affect my obesity and insulin resistance?

Adipose tissue macrophages (ATMs) are immune cells in your fat tissue. In obesity, these cells change from a calm, anti-inflammatory type to a pro-inflammatory type. This shift fuels chronic low-grade inflammation and makes your body less responsive to insulin, a condition called insulin resistance. Understanding how ATMs work helps explain why obesity and insulin resistance often go hand in hand.

What the research says

ATMs are central to the link between obesity and insulin resistance. In obesity, ATMs undergo metabolic reprogramming: their glucose, lipid, and amino acid pathways shift, driving them toward a pro-inflammatory phenotype that worsens insulin resistance ⁴. A 2025 study found that a protein called BNIP3 triggers mitophagy (a cleanup process for damaged mitochondria) in ATMs, which promotes a glycolytic shift and pro-inflammatory activation. When BNIP3 was removed in mice, it reduced fat tissue inflammation and improved insulin sensitivity ¹⁰. This suggests that targeting BNIP3 could be a future therapy.

Obesity also causes ATMs to accumulate bioactive lipids like ceramides and diacylglycerols, which further drive inflammation and insulin resistance ¹¹. Additionally, adipose tissue fibrosis (scarring) in obesity is linked to inflammation and metabolic dysfunction, and ATMs play a role in this remodeling ⁹. Genetic studies have identified insulin resistance loci that implicate inflammatory pathways in fat tissue, including those involving macrophages ⁶.

Other factors like reduced physical activity or microgravity can alter fat distribution and promote inflammation, which may also affect ATM behavior ². While some interventions like amiloride ⁵ or acupoint catgut embedding ¹ are being studied for obesity and insulin resistance, they do not directly target ATMs. The gut-brain axis and psychotropic medications can also influence metabolism, but their effects on ATMs are less clear ⁸.

What to ask your doctor

• Could my insulin resistance be related to inflammation in my fat tissue?
• Are there any treatments that target inflammation or immune cells in fat tissue?
• Would lifestyle changes like diet or exercise help reduce fat tissue inflammation?
• Should I be tested for markers of inflammation, such as C-reactive protein?
• Are there any clinical trials on new therapies for obesity-related inflammation?