Inflammation during obesity and aging contributes to impairments in adipose tissue leading to poor metabolic health. Consequently, obesity induces an inflammatory environment within adipose tissue that is associated with an irreversible cell cycle arrest known as cellular senescence. Likewise, this inflammatory environment is detrimental to the generation of new adipocytes, impairing the physiological role of white adipose tissue and damaging metabolic health. However, there is substantial evidence that reducing dietary protein intake, without reducing caloric intake, protects against HFD-induced obesity, improves glucose homeostasis, increases energy expenditure, and remodels adipose tissue. Our lab recently discovered that the effects of dietary protein restriction (DPR) require increases in the beneficial metabolic hormone Fibroblast Growth Factor 21 (FGF21), and that FGF21 mediates improvements in metabolic health by acting directly within the brain. Importantly, our data suggest that a key FGF21-dependent effect of protein restriction is the remodeling of white adipose tissue, and we hypothesize that this adipose tissue remodeling is a primary mediator of the improvements in metabolic health and lifespan. However, the specific changes that occur in adipose tissue which contribute to the beneficial metabolic effects of protein restriction are not well defined. Considering that obesity is associated with profound changes in adipose tissue, and that white adipose tissue is a critical endocrine mediator of energy expenditure and insulin sensitivity, it is likely that diet interventions such as DPR will reduce the metabolic insult cellular senescence and its markers, such as p16INK4a and the senescence-associated secretory phenotype (SASP), in adipose tissue. The goal of the current proposal is to determine if remodeling of adipose tissue by DPR reduces senescent cells, therefore reducing the SASP in WAT. This pilot and feasibly grant will test the central hypothesis that dietary protein restriction protects against the detrimental effects of senescent cells during obesity.

Public Health Relevance

The goal of the current supplemental Pennington/Louisiana NORC proposal is to determine if remodeling of adipose tissue by dietary protein restriction reduces senescent cells in the adipose tissue, therefore reducing the senescence-associated secretory phenotype leading to impaired metabolic health. This pilot and feasibly grant from a minority early stage investigator will test the central hypothesis that dietary protein restriction protects against the detrimental effects of senescent cells during obesity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
3P30DK072476-15S4
Application #
10192066
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Evans, Mary
Project Start
2005-07-01
Project End
2021-04-30
Budget Start
2020-05-01
Budget End
2021-04-30
Support Year
15
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Lsu Pennington Biomedical Research Center
Department
Type
Organized Research Units
DUNS #
611012324
City
Baton Rouge
State
LA
Country
United States
Zip Code
70808
Rose, Meredith H; Streisand, Randi; Aronow, Laura et al. (2018) Preliminary Feasibility and Acceptability of the Remote Food Photography Method for Assessing Nutrition in Young Children with Type 1 Diabetes. Clin Pract Pediatr Psychol 6:270-277
Broskey, Nicholas T; Obanda, Diana N; Burton, Jeffrey H et al. (2018) Skeletal muscle ceramides and daily fat oxidation in obesity and diabetes. Metabolism 82:118-123
Broskey, Nicholas T; Tam, Charmaine S; Sutton, Elizabeth F et al. (2018) Metabolic inflexibility in women with PCOS is similar to women with type 2 diabetes. Nutr Metab (Lond) 15:75
Marlatt, Kara L; White, Ursula A; Beyl, Robbie A et al. (2018) Role of resistant starch on diabetes risk factors in people with prediabetes: Design, conduct, and baseline results of the STARCH trial. Contemp Clin Trials 65:99-108
Staiano, Amanda E; Allen, Andrew T; Fowler, Whitney et al. (2018) State Licensing Regulations on Screen Time in Childcare Centers: An Impetus for Participatory Action Research. Prog Community Health Partnersh 12:101-109
Forney, Laura A; Stone, Kirsten P; Wanders, Desiree et al. (2018) The role of suppression of hepatic SCD1 expression in the metabolic effects of dietary methionine restriction. Appl Physiol Nutr Metab 43:123-130
Katzmarzyk, Peter T; Martin, Corby K; Newton Jr, Robert L et al. (2018) Promoting Successful Weight Loss in Primary Care in Louisiana (PROPEL): Rationale, design and baseline characteristics. Contemp Clin Trials 67:1-10
Fazzino, Tera L; Martin, Corby K; Forbush, Kelsie (2018) The Remote Food Photography Method and SmartIntake App for the Assessment of Alcohol Use in Young Adults: Feasibility Study and Comparison to Standard Assessment Methodology. JMIR Mhealth Uhealth 6:e10460
Most, Jasper; Gilmore, L Anne; Smith, Steven R et al. (2018) Significant improvement in cardiometabolic health in healthy nonobese individuals during caloric restriction-induced weight loss and weight loss maintenance. Am J Physiol Endocrinol Metab 314:E396-E405
Myers, Candice A; Martin, Corby K; Apolzan, John W (2018) Food cravings and body weight: a conditioning response. Curr Opin Endocrinol Diabetes Obes 25:298-302

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