Similar degrees of obesity induced by diet or aging cause strikingly different immunologic and metabolic outcomes

Krishna, Kanthi Bangalore; Stefanović-Račić, Maja; Dedousis, Nikolaos; Sipula, Ian; O’Doherty, Robert M.

doi:10.14814/phy2.12708

Cited by 23 publications

(27 citation statements)

References 43 publications

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“…; Krishna et al. ), despite this, species widespread use as a preclinical model of metabolic disease. Further, to the best of our knowledge, no information exists regarding the effect of sex on age‐related obesity and insulin resistance in mice.…”

Section: Introductionmentioning

confidence: 99%

The impact of age and sex on body composition and glucose sensitivity in C57BL/6J mice

et al. 2019

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A paucity of data exists regarding sex differences in age‐related obesity and insulin resistance, particularly in the preclinical murine model. The purpose of this study was to determine the effects of age and sex on insulin action and body composition in C57BL/6J mice. Aged (AG, 18 months old) male C57BL/6J mice, glucose tolerance was diminished compared to young (YG, 6 months old) male mice (Area Under Curve: 95,103 ± 6818 vs. 64,005 ± 2031, P = 0.002). However, there was no age‐related decline in glucose or insulin tolerance in females. Body composition analysis revealed that AG males had significantly greater body mass (42.2 ± 1.9 vs. 30.0 ± 0.4 g, P < 0.0001), fat mass (18.7 ± 2.0 vs. 3.3 ± 0.4 g, P < 0.0001), body fat (43.0 ± 3.0 vs. 11.0 ± 1.5%, P < 0.0001) than YG males. In AG females, body mass (32.8 ± 1.6 vs. 26.3 ± 0.9 g, P = 0.02) was higher, but fat mass (13.3 ± 2.0 vs. 9.5 ± 1.3 g, P = 0.24) and body fat (37.8 ± 4.8 vs. 35.5 ± 3.8%, P = 0.67) were similar when compared to YG females. AG males had significantly higher body mass (42.2 ± 1.9 vs. 32.8 ± 1.6 g, P = 0.001) and fat mass (18.7 ± 2.0 vs. 13.3 ± 2.0 g, P = 0.04) compared to AG females; however, body fat (43.0 ± 3.0 vs. 37.8 ± 4.8%, P = 0.28) was similar. Six weeks of treatment with MitoQ, a mitochondrial‐targeted antioxidant, did not reverse age‐related obesity in male mice. Surprisingly, obesity and insulin resistance appear to be reversed in the oldest of the old male mice (28 vs. 20 months). Our findings indicate that female mice, unlike males, are protected from age‐related obesity and insulin resistance.

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Section: Introductionmentioning

confidence: 99%

The impact of age and sex on body composition and glucose sensitivity in C57BL/6J mice

et al. 2019

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“…Furthermore, the aging-induced accumulation of islet T cells is not recapitulated by a similar degree of weight gain in diet-induced obese mice, and thus is not driven by obesity. This parallels the divergent immune cell profiles in adipose tissue of aged versus obese mice (31). Similarly, the metabolic outcomes of aging and diet-induced obesity in mice are different, with aging resulting in increased insulin secretion and ultimately improved glucose tolerance in advanced age mice, whereas diet-induced obesity impairs insulin secretion and glucose tolerance.…”

Section: Discussionmentioning

confidence: 85%

“…Aging is also associated with inflammation in adipose tissue promoting insulin resistance, though the changes are distinct from those of obesity. T cells accumulate in aged visceral adipose tissue whereas the total number of macrophages is relatively unperturbed (21,(29)(30)(31), and unlike in diet-induced obesity, adipose tissue T regulatory cells accumulate and contribute to worsening glucose homeostasis during aging (21,29). B2 cells also accumulate in WAT with age, and contribute to insulin resistance and glucose intolerance (32).…”

Section: Introductionmentioning

confidence: 99%

T cells are present in non-diabetic islets and accumulate during aging

Denroche

Miard

Sallé-Lefort

et al. 2020

Preprint

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BackgroundThe resident immune population of pancreatic islets has roles in islet development, beta cell physiology, and the pathology of diabetes. These roles have largely been attributed to islet macrophages, comprising 90% of islet immune cells (in the absence of islet autoimmunity), and, in the case of type 1 diabetes, to infiltrating autoreactive T cells. In adipose, tissue-resident and recruited T and B cells have been implicated in the development of insulin resistance during diet-induced obesity and aging, but whether this is paralleled in the pancreatic islets is not known. Here, we investigated the non-macrophage component of resident islet immune cells in islets isolated from C57BL/6J male mice during aging (3 to 24 months of age) and following diet-induced obesity (12 weeks 60% high fat diet). Immune cells were also examined by flow cytometry in cadaveric non-diabetic human islets.ResultsImmune cells comprised 2.7 ± 1.3% of total islet cells in non-diabetic mouse islets, and 2.3 ± 1.7% of total islet cells in non-diabetic human islets. In 3-month old mice on standard diet, B and T cells each comprised approximately 2-4% of the total islet immune cell compartment, and approximately 0.1% of total islet cells. A similar amount of T cells were present in non-diabetic human islets. Islet T cells were comprised of CD8-positive, CD4-positive, and regulatory T cells. Interestingly, while islet B cells and macrophage numbers were unaltered by age, the number of islet T cells increased linearly (R2=0.9902) with age from 0.10 ± 0.05% (3 months) to 0.38 ±0.11% (24 months) of islet cells. This increase was uncoupled from body weight, and was not phenocopied by a degree similar weight gain induced by high fat diet in mice.ConclusionsThis study reveals that T cells are a part of the normal islet immune population in mouse and human islets, and that they accumulate in islets during aging in a body weight-independent manner. Though comprising only a small subset of the immune cells within islets, islet T cells may play a role in the physiology of islet aging.

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“…Lei et al () recruited 793 women and 1091 men aged 20–40 years and concluded that age influences the body fat mass and other anthropometric indices. Furthermore, aging influences the whole organism, such as gastric emptying, intestinal absorption and metabolism (Krishna, Stefanovic‐Racic, Dedousis, Sipula, & O'Doherty, ; Santos, ), so age may have influenced the findings.…”

Section: Discussionmentioning

confidence: 99%

Clinical application of a cocoa and unripe banana flour beverage for overweight women with abdominal obesity: Prospective, double-blinded and randomized clinical trial

Vieira

Lomeu

Moreira

et al. 2017

Journal of Food Biochemistry

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Objective To assess the effect of a cocoa and unripe banana flour beverage (UBF) on fecal short‐chain fatty acids (SCFA), gastrointestinal symptoms, fecal characteristics and inflammation, in overweight women with abdominal adiposity. METHODS This prospective, double‐blinded, randomized clinical trial involved 60 female volunteers aged between 20 and 50 years. One group received a cocoa beverage (n = 30) and one group received a cocoa and UBF beverage (n = 30), for 6 weeks. Intestinal microbiota was indirectly assessed by consistency, shape, and color of feces, determination of fecal SCFA, and gastrointestinal symptoms. RESULTS Both beverages increased the production of propionic acid (p < .05) and decreased gastrointestinal symptoms (p < .05). The cocoa beverage decreased indigestion (p < .05) and the pro‐inflammatory cytokine, IL‐17. CONCLUSION Cocoa and cocoa with UBF beverages decreased the symptoms of dyspepsia, improved gastrointestinal symptoms, and increased production of propionic acid, favoring healthy intestinal microbiota. Only the cocoa beverage showed an anti‐inflammatory effect. Practical applications Unripe banana flour and cocoa have been widely used to decrease cardiovascular risk, by improving inflammatory parameters and gastrointestinal symptoms. However, the interaction between these two food ingredients and the implication of their interaction on human health remains unknown. Important health benefits may be achieved by assessing the synergism or antagonism of functional foods, particularly when they coexist in the same product. This study aims to attract the interest of the scientific community to conduct more studies on functional bioavailability. Both unripe banana flour and cocoa can have therapeutic potential but it may not be a good idea to associate them. This article provides relevant information to the scientific and broader community regarding the preparation of these foods, to maximize their health benefits on a daily basis, and, additionally, offers the food industry valuable knowledge that can be used to develop healthier food products.

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Similar degrees of obesity induced by diet or aging cause strikingly different immunologic and metabolic outcomes

Cited by 23 publications

References 43 publications

The impact of age and sex on body composition and glucose sensitivity in C57BL/6J mice

The impact of age and sex on body composition and glucose sensitivity in C57BL/6J mice

T cells are present in non-diabetic islets and accumulate during aging

Clinical application of a cocoa and unripe banana flour beverage for overweight women with abdominal obesity: Prospective, double-blinded and randomized clinical trial

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