Adaptive immune cells shape obesity-associated type 2 diabetes mellitus and less prominent comorbidities

Sara SantaCruz-Calvo, Leena Bharath, Gabriella Pugh, Lucia SantaCruz-Calvo, Raji Rajesh Lenin, Jenny Lutshumba, Rui Liu, Adam D. Bachstetter, Beibei Zhu, Barbara S. Nikolajczyk

Research output: Contribution to journalReview articlepeer-review

43 Scopus citations


Obesity and type 2 diabetes mellitus (T2DM) are increasing in prevalence owing to decreases in physical activity levels and a shift to diets that include addictive and/or high-calorie foods. These changes are associated with the adoption of modern lifestyles and the presence of an obesogenic environment, which have resulted in alterations to metabolism, adaptive immunity and endocrine regulation. The size and quality of adipose tissue depots in obesity, including the adipose tissue immune compartment, are critical determinants of overall health. In obesity, chronic low-grade inflammation can occur in adipose tissue that can progress to systemic inflammation; this inflammation contributes to the development of insulin resistance, T2DM and other comorbidities. An improved understanding of adaptive immune cell dysregulation that occurs during obesity and its associated metabolic comorbidities, with an appreciation of sex differences, will be critical for repurposing or developing immunomodulatory therapies to treat obesity and/or T2DM-associated inflammation. This Review critically discusses how activation and metabolic reprogramming of lymphocytes, that is, T cells and B cells, triggers the onset, development and progression of obesity and T2DM. We also consider the role of immunity in under-appreciated comorbidities of obesity and/or T2DM, such as oral cavity inflammation, neuroinflammation in Alzheimer disease and gut microbiome dysbiosis. Finally, we discuss previous clinical trials of anti-inflammatory medications in T2DM and consider the path forward.

Original languageEnglish
Pages (from-to)23-42
Number of pages20
JournalNature Reviews Endocrinology
Issue number1
StatePublished - Jan 2022

Bibliographical note

Funding Information:
The authors acknowledge the support of R01DK108056 (B.S.N.), U01DE025383 (B.S.N.), R56AG069685 (B.S.N.), R01NS103785 (A.D.B.) and the TRIAD 5T32AG057461 (J.L.).

Publisher Copyright:
© 2021, Springer Nature Limited.

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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