Review

Immunologic and endocrine functions of adipose tissue: implications for kidney disease

Published online:

Abstract

Excess adiposity can induce adverse sequelae in multiple cell types and organ systems. The transition from the lean to the obese state is characterized by fundamental cellular changes at the level of the adipocyte. These changes affect the local microenvironment within the respective adipose tissue but can also affect nonadipose systems. Adipocytes within fat pads respond to chronic nutrient excess through hyperplasia or hypertrophy, which can differentially affect interorgan crosstalk between various adipose depots and other organs. This crosstalk is dependent on the unique ability of the adipocyte to coordinate metabolic adjustments throughout the body and to integrate responses to maintain metabolic homeostasis. These actions occur through the release of free fatty acids and metabolites during times of energy need — a process that is altered in the obese state. In addition, adipocytes release a wide array of signalling molecules, such as sphingolipids, as well as inflammatory and hormonal factors (adipokines) that are critical for interorgan crosstalk. The interactions of adipose tissue with the kidney — referred to as the adipo–renal axis — are important for normal kidney function as well as the response of the kidney to injury. Here, we discuss the mechanistic basis of this interorgan crosstalk, which clearly has great therapeutic potential given the increasing rates of chronic kidney disease secondary to obesity and type 2 diabetes mellitus.

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Acknowledgements

The authors are supported by US National Institutes of Health (NIH) Grants R01-DK086629, R01-DK55758, P01-DK088761 and P01-AG051459 as well as by an unrestricted grant from the NovoNordisk Foundation.

Author information

Affiliations

  1. Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390–8549, USA.

    • Qingzhang Zhu
    •  & Philipp E. Scherer
  2. Touchstone Diabetes Center, Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390–8549, USA.

    • Philipp E. Scherer

Authors

  1. Search for Qingzhang Zhu in:

  2. Search for Philipp E. Scherer in:

Contributions

Both authors researched the data for the article, discussed its content and contributed to the writing and editing of the manuscript before submission.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Philipp E. Scherer.

Glossary

Beiging

A biological process that often occurs under cold stress or β-adrenergic stimulation to increase heat production, during which white adipose tissue switches from a unilocular to a multilocular phenotype (with more beige adipocytes).

M2-like macrophages

So-called alternatively activated macrophages that secrete cytokines that decrease inflammation.

M1-like macrophages

M1-polarized macrophages that release cytokines that encourage inflammation.

Unilocular

White adipocytes that display unilocular features, with a single large lipid droplet in the cytoplasm.

Multilocular

Brown and beige adipocytes that display a multilocular phenotype, with many small lipid droplets in the cytoplasm.

Dominant isoform

The major isoform with the most abundant expression within a protein family.

Acetylation

A type of post-translational histone modification that facilitates or inhibits the binding of a protein complex to its histone-binding site via remodelling of the chromatin structure, resulting in altered gene expression.

Monoubiquitylation

A type of post-translational histone modification; some histones, such as histone 2A, can be monoubiquitylated by adding a ubiquitin unit, thus regulating gene transcription by acting on the chromatin structure.

Leptin resistance

A condition that is often found in obesity and diabetes, in which leptin loses its anorectic functions in the brain despite high circulating levels of the hormone.

Uraemic toxin

Uraemic toxins are a group of uraemic retention solutes found in uraemic syndrome that are otherwise excreted by healthy kidneys.

Berberine

A compound found in herbs that increases adiponectin levels and activates 5′-AMP-activated protein kinase catalytic subunit α-1 (PRKAA1; also known as AMPK) and has anti-inflammatory and antidiabetic properties.

Sphingolipids

A class of lipids that can be part of cellular membranes. Moreover, sphingolipids and their metabolites, such as ceramides, sphingosine and sphingosine-1-phosphate, are signalling molecules and are involved in multiple diseases, including obesity, diabetes, cardiovascular disease, cancer and kidney disease.