Dwight Klemm PhD

Title: Principal Investigator; Professor, Pulmonary Sciences

Contact: dwight.klemm@cuanschutz.edu

University of Colorado webpage

Personal Statement
I have worked in adipocyte biology for over 25 years. During the first 14 years I was focused on transcriptional regulation of adipogenesis and adipocyte survival. In 2004 I initiated studies to determine whether non-tissue resident progenitor cells traffic to adipose tissue and generate new adipocytes. My laboratory was the first to demonstrate that some adipocytes are produced from progenitors cells that have a hematopoietic rather than mesenchymal origin. We subsequently demonstrated that these unique adipocytes are 1) also produced in humans, 2) higher in female rather than male mice, 3) characterized by a proinflammatory, but low metabolic gene expression profile, and 4) produced from adipose tissue macrophage. Preliminary studies described in this proposal indicate that the highest number of these potentially detrimental adipocytes is found in pericardial adipose tissue. In 2009 I joined the faculty of the Gates Center for Center Regenerative Medicine and Stem Biology.

Research Interest

I was a Research Biologist and Director of Basic Research for the Pulmonary and Critical Care Section of the Veterans Administration Eastern Colorado Health Care System (VA ECHCS) from 2001 to 2008, and currently serve as a Research Biologist in the Geriatric Research, Education and Clinical Center (GRECC) at the same VA facility since 2016. I am also a professor at the University of Colorado Anschutz Medical Campus where I serve as co-director of the Obesity Cell Biology Program of the Colorado Obesity Research Institute. In this capacity I have priority access to the institute’s Energy Balance Core, Metabolic Core and Cell Biology Core. I also serve as Associate Director of our Specialized Center of Research (SCOR) on aging, gonadal hormones and obesity. Given my expertise in adipocyte and stem cell biology, our initial description and continued characterization of bone marrow-derived adipocytes, and access to state-of-the-art core facilities at VA ECHCS and University of Colorado, my laboratory is uniquely suited to complete the proposed studies.

Grants & Funding

Diminished Sex Hormone Levels Stimulate Production of Inflammatory Bone Marrow-Derived Adipocytes

Obesity is prevalent among US military Veterans and linked to an increased incidence of cardiovascular disease, diabetes, pulmonary disorders, and certain forms of cancer. As the veteran population ages, diminished production of the primary sex hormone, estrogen, promotes fat accumulation in menopausal women.
We discovered a subpopulation of adipocytes in humans and mice termed bone marrow-derived adipocytes (BMDAs) that exhibit an inflammatory character. These unique adipocytes are more abundant in female than male mice. They are increased by the loss of estrogen in female mice. These observations led us to hypothesize that BMDAs provide a link between sex hormone-related changes in adiposity and body-wide inflammation. 
This project will test this hypothesis in mice in which estrogen signaling is suppressed and in which BMDAs and their progenitors are specifically ablated. Understanding the mechanisms by which sex hormones regulate BMDA and progenitor production holds the potential for therapies to prevent menopausal diseases in aging female veterans.
Investigator: Dwight Klemm
Funder: Veterans Affairs
NIH website
Publications of note:
— Hematopoietic Stem Cell-Derived Adipocytes Modulate Adipose Tissue Cellularity, Leptin Production and Insulin Responsiveness in Female Mice
— Hematopoietic stem cells produce intermediate lineage adipocyte progenitors that simultaneously express both myeloid and mesenchymal lineage markers in adipose tissue
— Modulation of Energy Expenditure by Estrogens and Exercise in Women

Integrin signaling promotes production of adipocytes from hematopoietic cells

Obesity is a major medical problem for which there are few effective therapies. 
This project will investigate the processes and events that control the production of potentially harmful fat cells. Successful completion of these studies will identify new targets for controlling the production of harmful fat-storing cells and prevent fat-related chronic disease.
Investigator: Dwight Klemm
Funder: National Institute of Diabetes and Digestive and Kidney Diseases
NIH website
Publications of note:
— Hematopoietic Stem Cell-Derived Adipocytes Modulate Adipose Tissue Cellularity, Leptin Production and Insulin Responsiveness in Female Mice
— Hematopoietic stem cells produce intermediate lineage adipocyte progenitors that simultaneously express both myeloid and mesenchymal lineage markers in adipose tissue

Recent Publications

2024

Libby AE, Solt C, Jackman M, Sherk V, Foright RM, Johnson GC, Nguyen TT, Breit M, Hulett N, Rudolph M, Roberson PA, Wellberg E, Jambal P, Scalzo RL, Higgins J, Kumar TR, Wierman ME, Pan Z, Shankar K, Klemm DJ, Moreau KL, Kohrt WM, MacLean PS. Effects of Follicle Stimulating Hormone on Energy Balance and Tissue Metabolic Health After Loss of Ovarian Function. Am J Physiol Endocrinol Metab. 2024 Mar 27. doi: 10.1152/ajpendo.00400.2023. Epub ahead of print. 
PMID: 38536037.

2022

Gavin KM, Sullivan TM, Maltzahn JK, Jackman MR, Libby AE, MacLean PS, Kohrt WM, Majka SM, Klemm DJ. Hematopoietic Stem Cell-Derived Adipocytes Modulate Adipose Tissue Cellularity, Leptin Production and Insulin Responsiveness in Female Mice. Front Endocrinol (Lausanne). 2022 Jun 3;13:844877. doi: 10.3389/fendo.2022.844877. PMCID: PMC9203959. 
PMID: 35721743.