Decreased NK cell functions in obesity can be reactivated by fat mass reduction

Jahn, Janine; Spielau, Marco; Brandsch, Corinna; Stangl, Gabriele I.; Delank, Karl‐Stefan; Bähr, Ina; Berreis, Tobias; Wrann, Christiane D.; Kielstein, Heike

doi:10.1002/oby.21229

Cited by 58 publications

(56 citation statements)

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“…In addition, investigations provided evidence that impaired NK cell activity in obesity can be improved by reduction of fat and energy intake, weight stability, and weight loss after bariatric surgery or a moderate dietary and exercise program [20, 21, 53–56]. Therefore, prevention of overweight and fat mass reduction in obesity by physical training or caloric restriction can attenuate the colon cancer risk by improving the NK cell functionality.…”

Section: Discussionmentioning

confidence: 99%

“…Fluorescence-activated cell sorter (FACS) analyses were performed as described earlier [21]. The following mouse anti-rat antibodies were used: CD3 APC, CD4 PE-Cy 7, CD8a PE, CD45RA FITC, and CD161a PE (BD Biosciences, San Diego, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, the disturbed NK cell functionality could be ameliorated by transfer of NK cells to a normal weight metabolic environment in rats [19]. Furthermore, the altered NK cell activity could be reactivated after weight loss and fat mass reduction after bariatric surgery or a combined exercise and dietary program [20, 21]. …”

Section: Introductionmentioning

confidence: 99%

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Diet-Induced Obesity Is Associated with an Impaired NK Cell Function and an Increased Colon Cancer Incidence

Bähr

Goritz

Doberstein

et al. 2017

Journal of Nutrition and Metabolism

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Obesity is associated with an increased colon cancer incidence, but underlying mechanisms remained unclear. Previous studies showed altered Natural killer (NK) cell functions in obese individuals. Therefore, we studied the impact of an impaired NK cell functionality on the increased colon cancer risk in obesity. In vitro investigations demonstrated a decreased IFN-γ secretion and cytotoxicity of human NK cells against colon tumor cells after NK cell preincubation with the adipokine leptin. In addition, leptin incubation decreased the expression of activating NK cell receptors. In animal studies, colon cancer growth was induced by injection of azoxymethane (AOM) in normal weight and diet-induced obese rats. Body weight and visceral fat mass were increased in obese animals compared to normal weight rats. AOM-treated obese rats showed an increased quantity, size, and weight of colon tumors compared to the normal weight tumor group. Immunohistochemical analyses demonstrated a decreased number of NK cells in spleen and liver in obesity. Additionally, the expression levels of activating NK cell receptors were lower in spleen and liver of obese rats. The results show for the first time that the decreased number and impaired NK cell function may be one cause for the higher colon cancer risk in obesity.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Diet-Induced Obesity Is Associated with an Impaired NK Cell Function and an Increased Colon Cancer Incidence

Bähr

Goritz

Doberstein

et al. 2017

Journal of Nutrition and Metabolism

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“…Leptin also upregulates the secretion of proinflammatory cytokines (TNF- α , IL-6, and IL-12) by macrophages [25, 52, 53]. …”

Section: Adipokines and Their Receptorsmentioning

confidence: 99%

Adipokine Contribution to the Pathogenesis of Osteoarthritis

Azamar-Llamas

Hernández-Molina

Ramos-Ávalos

et al. 2017

Mediators of Inflammation

134

115

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Recent studies have shown that overweight and obesity play an important role in the development of osteoarthritis (OA). However, joint overload is not the only risk factor in this disease. For instance, the presence of OA in non-weight-bearing joints such as the hand suggests that metabolic factors may also contribute to its pathogenesis. Recently, white adipose tissue (WAT) has been recognized not only as an energy reservoir but also as an important secretory organ of adipokines. In this regard, adipokines have been closely associated with obesity and also play an important role in bone and cartilage homeostasis. Furthermore, drugs such as rosuvastatin or rosiglitazone have demonstrated chondroprotective and anti-inflammatory effects in cartilage explants from patients with OA. Thus, it seems that adipokines are important factors linking obesity, adiposity, and inflammation in OA. In this review, we are focused on establishing the physiological mechanisms of adipokines on cartilage homeostasis and evaluating their role in the pathophysiology of OA based on evidence derived from experimental research as well as from clinical-epidemiological studies.

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“…Additionally, obese patients who lost body weight by bariatric surgery or by exercise training and nutrition courses could reverse their impaired NK cell activity and NK cell-mediated cytokine synthesis [7, 18]. This indicates that there might be a close interaction between impaired NK cell functions in obese individuals and the increased risk for cancer in obesity.…”

Section: Introductionmentioning

confidence: 99%

Significantly enhanced lung metastasis and reduced organ NK cell functions in diet-induced obese rats

et al. 2017

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BackgroundObesity was identified as a major risk factor for malignant diseases, but underlying mechanisms remain unclear. Natural killer (NK) cells, a pivotal aspect of innate immunity, are capable of identifying and killing virally infected and tumor cells. Previous studies have shown altered NK cell functions in obesity, and the current study aimed to investigate the relationship between altered NK cell functions and increased cancer risk in obesity.MethodsTo induce obesity male F344-rats received a high-fat diet (34% fat) or a control diet (4% fat). Thereafter, syngeneic mammary adenocarcinoma cells (MADB106) or a vehicle were intravenously (i.v.) injected. 15 min after injection, half of each group of rats were killed, lungs removed and immunohistochemically stained. Numbers of NK cells, MADB106 cells and NK cell-tumor cell interactions were quantified. Twenty-one days after tumor-cell injection the other half group of rats was killed and lung metastases were counted and relative mRNA concentrations of different NK cell receptors were determined.ResultsAfter short-term MADB106-challenge, DIO fed animals showed significantly decreased NK cell numbers in the blood and NK cell-tumor cell interactions in the lung as compared to their control littermates. Twenty-one days after MADB106 injection, the lungs of the DIO fed rats showed significantly more lung metastases compared to control animals, accompanied by reduced relative mRNA concentrations of the activating NK cell receptor NKG2D.ConclusionsWe conclude that induction of obesity in F344-rats leads to reduced lung NK cell function against tumor cells and results in significantly enhanced lung metastasis as compared to lean animals. It can be hypothesized that obesity-induced altered NK cell functions play an important role in cancer growth and metastasis.Electronic supplementary materialThe online version of this article (doi:10.1186/s40608-017-0161-5) contains supplementary material, which is available to authorized users.

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Decreased NK cell functions in obesity can be reactivated by fat mass reduction

Cited by 58 publications

References 38 publications

Diet-Induced Obesity Is Associated with an Impaired NK Cell Function and an Increased Colon Cancer Incidence

Diet-Induced Obesity Is Associated with an Impaired NK Cell Function and an Increased Colon Cancer Incidence

Adipokine Contribution to the Pathogenesis of Osteoarthritis

Significantly enhanced lung metastasis and reduced organ NK cell functions in diet-induced obese rats

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