Obesity and Fat Metabolism in HIV Infected Individuals

Event Details

Background

Obesity is emerging as a critical factor in the pathogenesis of HIV and of its non-infectious co-morbidities. Conserved intracellular pathways link the biology of T cell metabolism, the immune response, and diabetes and a picture is beginning to emerge that suggests that obesity is both a consequence and a cause of immune activation. Increased immune activation is associated with the non-infectious comorbidities seen in individuals living with HIV. The origins of this chronic inflammatory condition are multifactorial, but one pathway relates to the loss of gut-associated lymphoid tissue, the disruption of the GI epithelial barrier and resultant microbial translocation. There is also a growing understanding that fat is an immunologically active tissue. HIV acts directly on adipose cells; specific HIV viral products affect adipocyte differentiation which may be independent of plasma viremia. These effects may pre-dispose individuals to the development of obesity and alter expression of pro-inflammatory cytokines. Altered expression of proinflammatory cytokines likely pre-disposes HIV-infected individuals to excess morbidity and mortality. For example, leptin, an adipokine produced by adipose tissue, has altered expression in people living with HIV and is a proinflammatory molecule with important immunological regulatory effects. Women with HIV may also be more adversely affected by these interactions than men. These discoveries have implications that stretch far beyond HIV.

Objectives

• An Action Plan with specific recommendations for future obesity research in HIV
• Identification of research gaps, needs, opportunities, and plans to facilitate progress and catalyze new research directions.
• Knowledge exchange and the development of further collaborations and joint collaborations to advance the field.

Co-Sponsors/Organizers

National Institute of Allergy and Infectious Diseases

National Institute of Diabetes and Digestive and Kidney Diseases

National Institutes of Health Office of AIDS Research

National Institutes of Health Office of Research on Women’s Health

Registration Deadline

May 14, 2018

Agenda

May 22, 2018

8:00 a.m. – 8:25 a.m.

Registration

8:25 a.m. – 8:30 a.m.

Welcome and Opening Remarks
Griffin Rodgers, Director, National Institute of Diabetes and Digestive and Kidney Diseases
Catherine Godfrey, National Institute of Allergy and Infectious Diseases
Andrew Bremer, National Institute of Diabetes and Digestive and Kidney Diseases

Session 1: Overview – Setting the Stage

Chair: Peter Hunt, University of California, San Francisco

Session Overview:

Brown vs beige fat; generalized obesity vs dysfunctional adipose tissue

Lifespan issues

8:30 a.m. – 9:00 a.m.

Overview of the underlying biology of immune activation linking it to obesity
Clovis Palmer, Burnet Institute

9:00 a.m. – 9:30 a.m.

Epigenetic link – in utero issues
Mary-Elizabeth Patti, Joslin Diabetes Center

9:30 a.m. – 10:00 a.m.

Fat types, distribution, sex differences, age differences, racial and ethnic differences
Aaron Cypess, National Institute of Diabetes and Digestive and Kidney Diseases

10:00 a.m. – 10:30 a.m.

Group Discussion

10:30 a.m. – 10:45 a.m.

Break

Session 2: It’s the Virus!

Co-Chairs: Todd Brown, Johns Hopkins University
Roger Paredes, IrsiCaixa AIDS Research Institute

Session Overview:

Relationship between HIV and its viral products and fat

10:45 a.m. – 11:15 a.m.

HIV viral products and the immunometabolism
Dorothy Lewis, The University of Texas Health Science Center at Houston

11:15 a.m. – 11:45 a.m.

miRNA, dicer and adipose tissue in HIV: novel pathways of fat regulation and organ specific cross-talk in HIV
Steve Grinspoon, Massachusetts General Hospital

11:45 a.m. – 12:00 p.m.

Fat and HIV persistence, role of fat metabolism and inflammation
Marta Giralt, University of Barcelona

12:00 p.m. – 12:30 p.m.

Group Discussion

12:30 p.m. – 1:30 p.m.

Lunch

Session 3: Immune and Metabolic Interactions

Co-Chairs: Steve Grinspoon, Massachusetts General Hospital
Jason Baker, University of Minnesota

Session Overview:

What WBCs are in fat? (M1, M2, Tregs, T effectors, NK cells, innate immune lymphocytes, and possibly even B-cells)

The adipocyte as a monocyte origin cell

1:30 p.m. – 1:50 p.m.

Adipose tissue function, dysfunction, and fat fibrosis. What does this all mean?
Suneil Koliwad, University of California San Francisco

1:50 p.m. – 2:10 p.m.

Fat as an immunologically active tissue: Defining the scope and cell types
Alyssa Hasty, Vanderbilt University School of Medicine

2:10 p.m. – 2:30 p.m.

Role of leptin and other adipokines in HIV infection and HIV-related obesity
John Koethe, Vanderbilt University

2:30 p.m. – 3:00 p.m.

Group Discussion

3:00 p.m. – 3:15 p.m.

Break

Session 4: GI Tract and Adipocyte Interactions

Co-Chairs: Rohit Loomba, University of California San Diego
Netanya Utay, University of Texas Houston

Session Overview:

The interplay between HIV and the GI tract, adipose tissue, and the liver

Other microbial “players” involved in mediating interactions between HIV and tissues

3:15 p.m. – 3:35 p.m.

GI tract barrier breakdown and adipocyte inflammation
Janet Lo, Massachusetts General Hospital

3:35 p.m. – 3:55 p.m.

Microbiome and products of microbial metabolism
Yasmine Belkaid, National Institute of Allergy and Infectious Diseases

3:55 p.m. – 4:15 p.m.

Liver disease/fatty liver, function of total fat, dysfunctional adipose tissue, and a depot that can’t handle it…Difference between HIV and non-HIV
Colleen Hadigan, National Institute of Allergy and Infectious Diseases

4:15 p.m. – 5:15 p.m.

Group Discussion

5:15 p.m.

Adjourn

May 23, 2018

8:00 a.m. – 8:15 a.m.

Recap of Day 1

Session 5: Pharmacology and Treatment of Obesity

Chair: Jordan Lake, University of Texas Health Science Center

Session Overview:

Non-viral effects of current HIV therapy

Viral and non-viral considerations for future HIV therapies

8:15 a.m. – 8:35 a.m.

ART effect on fat quantity and quality
Grace McComsey, University Hospitals Health System and Case Western Reserve University

8:35 a.m. – 8:55 a.m.

Metformin
Alex Soukas, Center for Genomic Medicine

8:55 a.m. – 9:15 a.m.

Other treatment options in the pipeline
Mark Febbraio, Garvan Institute for Medical Research

9:15 a.m. – 10:15 a.m.

Group Discussion

10:15 a.m. – 10:30 a.m.

Break

Session 6: How do we translate this information to the clinic? What clinical trials are needed? What tools are needed?

Co-Chairs: Judith Currier, University of California Los Angeles
Grace Aldrovandi, University of California Los Angeles

Session Overview:

Moving the science forward

What clinical trials are needed?

What tools are needed?

10:30 a.m. – 10:50 a.m.

Measuring endpoints and outcomes
Caroline Apovian, Boston University School of Medicine

10:50 a.m. – 11:10 a.m.

What clinical trials are needed?
Turner Overton, University of Alabama School of Medicine

11:10 a.m. – 12:00 p.m.

Group Discussion

12:00 p.m. – 12:15 p.m.

Wrap-up and Next Steps
Catherine Godfrey, National Institute of Allergy and Infectious Diseases
Andrew Bremer, National Institute of Diabetes and Digestive and Kidney Diseases

12:15 p.m.

Adjourn