Immune-Deficient Pfp/Rag2−/− Mice Featured Higher Adipose Tissue Mass and Liver Lipid Accumulation with Growing Age than Wildtype C57BL/6N Mice

Winkler Winkler,Hempel Hempel,Burkhardt Burkhardt,Christ Christ,Hsu Hsu,Kühne Kühne,Gericke Gericke,Brückner Brückner,Erler Erler

doi:10.3390/cells8080775

Winkler Winkler, Hempel Hempel + Show 7 more

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https://doi.org/10.3390/cells8080775

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Abstract

Aging is a risk factor for adipose tissue dysfunction, which is associated with inflammatory innate immune mechanisms. Since the adipose tissue/liver axis contributes to hepatosteatosis, we sought to determine age-related adipose tissue dysfunction in the context of the activation of the innate immune system fostering fatty liver phenotypes. Using wildtype and immune-deficient mice, we compared visceral adipose tissue and liver mass as well as hepatic lipid storage in young (ca. 14 weeks) and adult (ca. 30 weeks) mice. Adipocyte size was determined as an indicator of adipocyte function and liver steatosis was quantified by hepatic lipid content. Further, lipid storage was investigated under normal and steatosis-inducing culture conditions in isolated hepatocytes. The physiological age-related increase in body weight was associated with a disproportionate increase in adipose tissue mass in immune-deficient mice, which coincided with higher triglyceride storage in the liver. Lipid storage was similar in isolated hepatocytes from wildtype and immune-deficient mice under normal culture conditions but was significantly higher in immune-deficient than in wildtype hepatocytes under steatosis-inducing culture conditions. Immune-deficient mice also displayed increased inflammatory, adipogenic, and lipogenic markers in serum and adipose tissue. Thus, the age-related increase in body weight coincided with an increase in adipose tissue mass and hepatic steatosis. In association with a (pro-)inflammatory milieu, aging thus promotes hepatosteatosis, especially in immune-deficient mice.

Highlights

Obesity is one of the most prevalent health problems worldwide, which has been attributed to changes in lifestyle by increasing food intake and/or reducing physical activity
The Age-Related Increase in Body Weight Coincided with a Disproportionate Increase in Adipose Tissue in Immune-Deficient, but Not Wildtype Mice
We showed an increase of the adipose tissue/body weight ratio with increasing age in immune-deficient, not wildtype mice

Summary

Introduction

Obesity is one of the most prevalent health problems worldwide, which has been attributed to changes in lifestyle by increasing food intake and/or reducing physical activity It is mostly associated with metabolic co-morbidities such as diabetes type 2 and non-alcoholic fatty liver diseases (NAFLD), which may progress to chronic inflammatory non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC) [1,2]. It became obvious that a considerable number of obese individuals remain insulin sensitive and lack cardiometabolic complications such as diabetes, dyslipidemia, and vascular disease. These so-called metabolically healthy obese (MHO) are not at higher health risks compared with the normal non-obese population. The underlying mechanisms, which discriminate MHO from metabolically unhealthy obese (MUO) are largely unknown, yet, seem to rely on different immune mechanisms in the context of adipose tissue metabolism at least in part [10,11]

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