Obesity alters immune and metabolic profiles: New insight from obese‐resistant mice on high‐fat diet

Boi, Shannon K.; Buchta, Claire M.; Pearson, Nicole A; Francis, Meghan B.; Meyerholz, David K.; Grobe, Justin L; Norian, Lyse A.

doi:10.1002/oby.21620

Cited by 54 publications

(48 citation statements)

References 40 publications

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“…Data from our laboratory demonstrates that diet-matching is possible in BALB/c mice since a portion of mice fed a HFD fail to gain weight and are metabolically similar to chow-fed, lean controls. 48 We refer to these HFD-fed lean mice as "obese-resistant". Therefore, strain-specific metabolic differences and potential diet effects should be considered when performing or interpreting studies examining the effects of murine DIO on immune function.…”

Section: Obesity Drives a Pro-inflammatory Host Environmentmentioning

confidence: 99%

Obesity and CD8 T cell metabolism: Implications for anti‐tumor immunity and cancer immunotherapy outcomes

Turbitt

Rosean

Weber

et al. 2020

Immunological Reviews

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Obesity is an established risk factor for many cancers and has recently been found to alter the efficacy of T cell–based immunotherapies. Currently, however, the effects of obesity on immunometabolism remain unclear. Understanding these associations is critical, given the fact that T cell metabolism is tightly linked to effector function. Thus, any obesity‐associated changes in T cell bioenergetics are likely to drive functional changes at the cellular level, alter the metabolome and cytokine/chemokine milieu, and impact cancer immunotherapy outcomes. Here, we provide a brief overview of T cell metabolism in the presence and absence of solid tumor growth and summarize current literature regarding obesity‐associated changes in T cell function and bioenergetics. We also discuss recent findings related to the impact of host obesity on cancer immunotherapy outcomes and present potential mechanisms by which T cell metabolism may influence therapeutic efficacy. Finally, we describe promising pharmaceutical therapies that are being investigated for their ability to improve CD8 T cell metabolism and enhance cancer immunotherapy outcomes in patients, regardless of their obesity status.

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Section: Obesity Drives a Pro-inflammatory Host Environmentmentioning

confidence: 99%

Obesity and CD8 T cell metabolism: Implications for anti‐tumor immunity and cancer immunotherapy outcomes

Turbitt

Rosean

Weber

et al. 2020

Immunological Reviews

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“…Female C57BL/6JRj mice (Janvier, France) were maintained in a specific pathogen-free facility at the University of Lübeck. Starting at the age of 4 weeks over a period of 12 weeks, mice were offered free access to either chow containing 12 kJ% from fat, 64…”

Section: Mice and Feedingmentioning

confidence: 99%

Short‐term high‐fat diet feeding protects from the development of experimental allergic asthma in mice

Schröder

Wiese

Ender

et al. 2019

Clin Experimental Allergy

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Background A close association between obesity and asthma has been described. The nature of this association remains elusive, especially with respect to allergic asthma. Controversial findings exist regarding the impact of short‐term high‐fat diet (HFD) feeding on the development of allergic asthma. Objective To delineate the impact of short‐term HFD feeding on the development of experimental allergic asthma. Methods Female C57BL/6JRJ mice were fed with a short‐term HFD or chow diet (CD) for 12 weeks. Allergic asthma was induced by intraperitoneal OVA/alum sensitization followed by repeated OVA airway challenges. We determined airway hyperresponsiveness (AHR) and pulmonary inflammation by histologic and flow cytometric analysis of immune cells. Furthermore, we assessed the impact of HFD on dendritic cell (DC)‐mediated activation of T cells. Results Female mice showed a mild increase in body weight accompanied by mild metabolic alterations. Upon OVA challenge, CD‐fed mice developed strong AHR and airway inflammation, which were markedly reduced in HFD‐fed mice. Mucus production was similar in both treatment groups. OVA‐induced increases in DC and CD4+ T‐cell recruitment to the lungs were significantly attenuated in HFD‐fed mice. MHC‐II expression and CD40 expression in pulmonary CD11b+ DCs were markedly lower in HFD‐fed compared to CD‐fed mice, which was associated in vivo with a decreased T helper (Th) 1/17 differentiation and Treg formation without impacting Th2 differentiation. Conclusions/clinical relevance These findings suggest that short‐term HFD feeding attenuates the development of AHR, airway inflammation, pulmonary DC recruitment and MHC‐II/CD40 expression leading to diminished Th1/17 but unchanged Th2 differentiation. Thus, short‐term HFD feeding and associated metabolic alterations may have protective effects in allergic asthma development.

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“…Total T-cell numbers, as well as cytotoxic CD8 + and CD4 + T cells are reported to be positively associated with BMI and the prevalence of MetS by some authors [19][20][21], but not by others [22,23]. Also, several studies find that BMI is inversely correlated with telomere length in T cells [13,24].…”

Section: Introductionmentioning

confidence: 99%

Effects of bariatric surgery on telomere length and T-cell aging

et al. 2019

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Background Obesity adversely affects health and is associated with subclinical systemic inflammation and features of accelerated aging, including the T-cell immune system. The presence of metabolic syndrome (MetS) may accelerate, while bariatric surgery might reverse these phenomena. To examine the effects of MetS and bariatric surgery on T-cell aging, we measured relative telomere length (RTL) and T-cell differentiation status in obese patients before and after bariatric surgery. Methods WHO II/III classified obese patients scheduled for bariatric surgery were included: 41 without MetS and 67 with MetS. RTL and T-cell differentiation status were measured in circulating CD4 + and CD8 + T cells via flow cytometry. T-cell characteristics were compared between patients with and without MetS prior to and at 3, 6, and 12 months after surgery considering effects of age, cytomegalovirus-serostatus, and weight loss. Results Thymic output, represented by numbers of CD31-expressing naive T cells, showed an age-related decline in patients with MetS. MetS significantly enhanced CD8 + T-cell differentiation. Patients with MetS had significant lower CD4 + RTL than patients without MetS. Within the first 6 months after bariatric surgery, RTL increased in CD4 + T cells after which it decreased at month 12. A decline in both thymic output and more differentiated T cells was seen following bariatric surgery, more pronounced in the MetS group and showing an association with percentage of body weight loss. Conclusions In obese patients, MetS results in attrition of RTL and accelerated T-cell differentiation. Bariatric surgery temporarily reverses these effects. These data suggest that MetS is a risk factor for accelerated aging of T cells and that MetS should be a more prominent factor in the decision making for eligibility for bariatric surgery.

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Obesity alters immune and metabolic profiles: New insight from obese‐resistant mice on high‐fat diet

Cited by 54 publications

References 40 publications

Obesity and CD8 T cell metabolism: Implications for anti‐tumor immunity and cancer immunotherapy outcomes

Obesity and CD8 T cell metabolism: Implications for anti‐tumor immunity and cancer immunotherapy outcomes

Short‐term high‐fat diet feeding protects from the development of experimental allergic asthma in mice

Effects of bariatric surgery on telomere length and T-cell aging

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