Negative legacy of obesity.
Kohsuke ShirakawaJin EndoYoshinori KatsumataTsunehisa YamamotoMasaharu KataokaSarasa IsobeNaohiro YoshidaKeiichi FukudaMotoaki SanoPublished in: PloS one (2017)
Obesity promotes excessive inflammation, which is associated with senescence-like changes in visceral adipose tissue (VAT) and the development of type 2 diabetes (T2DM) and cardiovascular diseases. We have reported that a unique population of CD44hi CD62Llo CD4+ T cells that constitutively express PD-1 and CD153 exhibit cellular senescence and cause VAT inflammation by producing large amounts of osteopontin. Weight loss improves glycemic control and reduces cardiovascular disease risk factors, but its long-term effects on cardiovascular events and longevity in obese individuals with T2DM are somewhat disappointing and not well understood. High-fat diet (HFD)-fed obese mice were subjected to weight reduction through a switch to a control diet. They lost body weight and visceral fat mass, reaching the same levels as lean mice fed a control diet. However, the VAT of weight reduction mice exhibited denser infiltration of macrophages, which formed more crown-like structures compared to the VAT of obese mice kept on the HFD. Mechanistically, CD153+ PD-1+ CD4+ T cells are long-lived and not easily eliminated, even after weight reduction. Their continued presence maintains a self-sustaining chronic inflammatory loop via production of large amounts of osteopontin. Thus, we concluded that T-cell senescence is essentially a negative legacy effect of obesity.
Keyphrases
- weight loss
- high fat diet
- glycemic control
- insulin resistance
- adipose tissue
- high fat diet induced
- bariatric surgery
- cardiovascular disease
- cardiovascular events
- roux en y gastric bypass
- gastric bypass
- weight gain
- body weight
- type diabetes
- blood glucose
- metabolic syndrome
- oxidative stress
- dna damage
- risk factors
- coronary artery disease
- endothelial cells
- physical activity
- skeletal muscle
- obese patients
- nk cells
- body mass index
- stress induced
- high resolution
- transcription factor
- cardiovascular risk factors