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Negative legacy of obesity.

ABSTRACT: 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.

SUBMITTER: Shirakawa K

PROVIDER: S-EPMC5657997 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Negative legacy of obesity.

Shirakawa Kohsuke K Endo Jin J Katsumata Yoshinori Y Yamamoto Tsunehisa T Kataoka Masaharu M Isobe Sarasa S Yoshida Naohiro N Fukuda Keiichi K Sano Motoaki M

PloS one 20171026 10

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, b ...[more]

PMID: 29073165

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Project description:BackgroundWe test a novel 'weight scarring' hypothesis which suggests that past obesity is associated with impairments in current psychological well-being and this increases risk of negative physical health outcomes associated with obesity. Across two nationally representative studies, we tested whether past obesity is associated with current psychological outcomes and whether these psychological outcomes explain the association between past obesity and subsequent early mortality.MethodsData were from the National Health and Nutrition Examination Survey (NHANES) (n = 29,047) and the Health and Retirement Study (HRS) (n = 11,998). Past obesity was defined based on maximum lifetime weight in NHANES and the highest weight from past study waves in the HRS. Across both studies, current depressive symptoms were analysed. A set of 10 additional well-being measures were combined to produce an 'index of impaired well-being' in HRS. Subsequent all-cause mortality was examined using National Deaths Index records in NHANES and household interviews in HRS. Linear or logistic regression, Cox proportional hazard regression, and causal mediation models were used.ResultsWe found that past obesity was associated with greater current depressive symptoms after controlling for current weight status and in analyses limited to those who were no longer classified as having obesity in NHANES (β = 0.17; 95% CI: 0.13, 0.22) and HRS (β = 0.20; 95% CI: 0.08, 0.31). In HRS, past obesity was also associated with a range of current negative psychological outcomes, including an index of impaired psychological well-being (β = 0.16; 95% CI: 0.05, 0.27). Past obesity was associated with a higher risk of early mortality in both NHANES and HRS (HR = 1.31; 95% CI: 1.16, 1.48 and HR = 1.34; 95% CI: 1.20, 1.50, respectively). Depressive symptoms explained 6% (95% CI: 0.01, 0.10) and 5% (95% CI: 0.01, 0.09) of the association between past obesity and premature mortality in NHANES and HRS, respectively. Impaired psychological well-being partly mediated the association between past obesity and premature mortality by 10% (95% CI: 0.04, 0.16) in HRS.ConclusionsOur findings suggest that there may be a psychological legacy of past obesity that is associated with raised mortality risk. Ensuring people with obesity receive psychological support even after experiencing weight loss may be important.

Project description:Soil respiration, the main ecosystem process that produces carbon dioxide into the atmosphere, is sensitive to extreme climatic events. The immediate, usually negative effect of droughts on soil respiration has often been observed, but the recovery of soil respiration following drought is rarely documented. Soil respiration can be reduced beyond the drought year if drought-induced changes suppress soil activity. Alternatively, reduction in soil respiration may be overcompensated in the subsequent years due to increased substrate input and soil moisture, resulting from plant dieback during drought. In addition, post-drought weather patterns may also affect the recovery of soil respiration. In a full-factorial grassland experiment, we combined an extreme (5 months) summer drought in 2014 with four levels of post-drought precipitation regimes, including severe (2 months) droughts, moderate (1 month) droughts, ambient weather, and water addition (four large rain events) in summers of 2015 and 2016. We measured soil respiration monthly between May and November, from 2013 to 2016. The extreme drought had an immediate strong negative effect, decreasing soil respiration by 50.8% in 2014 compared to the control plots, and it had a negative legacy effect in 2015 (14.5% reduction), but not in 2016. This legacy effect was unaffected by the post-drought precipitation regime. Moderate drought decreased soil respiration by 12.1% and 18.6%, while severe drought decreased soil respiration by 18.3% and 27.3% in 2015 and 2016, respectively, while water addition had no effect. Since soil water content in extreme drought plots recovered by 2015, we hypothesize that changes in soil biota and reduced root activity are responsible for extreme drought's long-term negative effects. Overall, our results highlight that extreme droughts may have negative effects on soil respiration well beyond the event, and thus the full effect on carbon cycling may be much larger than what is estimated solely based on the immediate effects.

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Negative legacy of obesity.

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Negative legacy of obesity.

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