Effects of Very Low Calorie Ketogenic Diet on the Orexinergic System, Visceral Adipose Tissue, and ROS Production

Background: Caloric restriction is a valid strategy to reduce the visceral adipose tissue (VAT) content in obese persons. Hypocretin-1 (orexin-A) is a neuropeptide synthesized in the lateral hypothalamus that strongly modulates food intake, thus influencing adipose tissue accumulation. Therapeutic diets in obesity treatment may combine the advantages of caloric restriction and dietary ketosis. The current study aimed to evaluate the effect of a very low calorie ketogenic diet (VLCKD) in a population of obese patients. Methods: Adiposity parameters and orexin-A serum profiling were quantified over an 8 week period. The effect of the VLCKD on reactive oxygen species (ROS) production and cell viability was evaluated, in vitro, by culturing Hep-G2 cells in the presence of VLCKD sera. Results: Dietary intervention induced significant effects on body weight, adiposity, and blood chemistry parameters. Moreover, a selective reduction in VAT was measured by dual-energy X-ray absorptiometry. Orexin-A levels significantly increased after dietary treatment. Hep-G2 cell viability was not affected after 24, 48, and 72 h incubation with patients’ sera, before and after the VLCKD. In the same model system, ROS production was not significantly influenced by dietary treatment. Conclusion: The VLCKD exerts a positive effect on VAT decrease, ameliorating adiposity and blood chemistry parameters. Furthermore, short-term mild dietary ketosis does not appear to have a cytotoxic effect, nor does it represent a factor capable of increasing oxidative stress. Finally, to the best of our knowledge, this is the first study that shows an effect of the VLCKD upon the orexinergic system, supporting the usefulness of such a therapeutic intervention in promoting obesity reduction in the individual burden of this disease.

Download Full-text

Monoamine oxidase is a source of oxidative stress in obese patients with chronic inflammation

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2019-0028 ◽

2019 ◽

Vol 97 (9) ◽

pp. 844-849 ◽

Cited By ~ 3

Author(s):

Adrian Sturza ◽

Sorin Olariu ◽

Mihaela Ionică ◽

Oana M. Duicu ◽

Adrian O. Văduva ◽

...

Keyword(s):

Oxidative Stress ◽

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Mesenteric Artery ◽

Vascular Reactivity ◽

Ros Production ◽

Obese Patients ◽

Quantitative Real Time Pcr ◽

Mao A ◽

Visceral Adipose

Obesity is an important preventable risk factor for morbidity and mortality from cardiometabolic disease. Oxidative stress (including in visceral adipose tissue) and chronic low-grade inflammation are the major underlying pathomechanisms. Monoamine oxidase (MAO) has recently emerged as an important source of cardiovascular oxidative stress. The present study was conducted to evaluate the role of MAO as contributor to reactive oxygen species (ROS) production in white adipose tissue and vessels harvested from patients undergoing elective abdominal surgery. To this aim, visceral adipose tissue and mesenteric artery branches were isolated from obese patients with chronic inflammation and used for organ bath, ROS production, quantitative real-time PCR, and immunohistology studies. The human visceral adipose tissue and mesenteric artery branches contain mainly the MAO-A isoform, as shown by the quantitative real-time PCR and immunohistology experiments. A significant upregulation of MAO-A, the impairment in vascular reactivity, and increase in ROS production were found in obese vs. non-obese patients. Incubation of the adipose tissue samples and vascular rings with the MAO-A inhibitor (clorgyline, 30 min) improved vascular reactivity and decreased ROS generation. In conclusion, MAO-A is the predominant isoform in human abdominal adipose and vascular tissues, is overexpressed in the setting of inflammation, and contributes to the endothelial dysfunction.

Download Full-text

Caloric Restriction Prevents Visceral Adipose Tissue Accumulation and Maintains Erectile Function in Aging Rats

Journal of Sexual Medicine ◽

10.1111/j.1743-6109.2012.02681.x ◽

2012 ◽

Vol 9 (9) ◽

pp. 2273-2283 ◽

Cited By ~ 6

Author(s):

M. Tina Maio ◽

Johanna L. Hannan ◽

Marina Komolova ◽

Michael A. Adams

Keyword(s):

Adipose Tissue ◽

Caloric Restriction ◽

Visceral Adipose Tissue ◽

Erectile Function ◽

Aging Rats ◽

Tissue Accumulation ◽

Visceral Adipose

Download Full-text

The effect of caloric restriction on the increase in senescence-associated T cells and metabolic disorders in aged mice

PLoS ONE ◽

10.1371/journal.pone.0252547 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0252547

Author(s):

Xiaoxiang Yan ◽

Natsumi Imano ◽

Kayoko Tamaki ◽

Motoaki Sano ◽

Ken Shinmura

Keyword(s):

Insulin Resistance ◽

T Cells ◽

Adipose Tissue ◽

T Cell ◽

Caloric Restriction ◽

Visceral Adipose Tissue ◽

Aged Mice ◽

Age Related ◽

Visceral Adipose

Aging is associated with functional decline in the immune system and increases the risk of chronic diseases owing to smoldering inflammation. In the present study, we demonstrated an age-related increase in the accumulation of Programmed Death-1 (PD-1)+ memory-phenotype T cells that are considered “senescence-associated T cells” in both the visceral adipose tissue and spleen. As caloric restriction is an established intervention scientifically proven to exert anti-aging effects and greatly affects physiological and pathophysiological alterations with advanced age, we evaluated the effect of caloric restriction on the increase in this T-cell subpopulation and glucose tolerance in aged mice. Long-term caloric restriction significantly decreased the number of PD-1+ memory-phenotype cluster of differentiation (CD) 4+ and CD8+ T cells in the spleen and visceral adipose tissue, decreased M1-type macrophage accumulation in visceral adipose tissue, and improved insulin resistance in aged mice. Furthermore, the immunological depletion of PD-1+ T cells reduced adipose inflammation and improved insulin resistance in aged mice. Taken together with our previous report, these results indicate that senescence-related T-cell subpopulations are involved in the development of chronic inflammation and insulin resistance in the context of chronological aging and obesity. Thus, long-term caloric restriction and specific deletion of senescence-related T cells are promising interventions to regulate age-related chronic diseases.

Download Full-text

Single-Cell RNA Sequencing of Visceral Adipose Tissue Leukocytes Reveals that Caloric Restriction Following Obesity Promotes the Accumulation of a Distinct Macrophage Population with Features of Phagocytic Cells

Immunometabolism ◽

10.20900/immunometab20190008 ◽

2019 ◽

Cited By ~ 4

Keyword(s):

Adipose Tissue ◽

Single Cell ◽

Rna Sequencing ◽

Caloric Restriction ◽

Visceral Adipose Tissue ◽

Phagocytic Cells ◽

Macrophage Population ◽

Single Cell Rna Sequencing ◽

Visceral Adipose

Download Full-text

The microenvironment of visceral adipose tissue and liver alter natural killer cell viability and function

Journal of Leukocyte Biology ◽

10.1189/jlb.5ab1115-493rr ◽

2016 ◽

Vol 100 (6) ◽

pp. 1435-1442 ◽

Cited By ~ 6

Author(s):

Melissa J. Conroy ◽

Vivienne Fitzgerald ◽

Suzanne L. Doyle ◽

Shauna Channon ◽

Zivile Useckaite ◽

...

Keyword(s):

Adipose Tissue ◽

Natural Killer Cell ◽

Cell Viability ◽

Natural Killer ◽

Visceral Adipose Tissue ◽

Killer Cell ◽

And Function ◽

Visceral Adipose

Download Full-text

Rapid Escalation of High-Volume Exercise during Caloric Restriction; Change in Visceral Adipose Tissue and Adipocytokines in Obese Sedentary Breast Cancer Survivors

Cancers ◽

10.3390/cancers13194871 ◽

2021 ◽

Vol 13 (19) ◽

pp. 4871

Author(s):

Carol J. Fabian ◽

Jennifer R. Klemp ◽

Nicholas J. Marchello ◽

Eric D. Vidoni ◽

Debra K. Sullivan ◽

...

Keyword(s):

Breast Cancer ◽

Adipose Tissue ◽

Cancer Survivors ◽

Caloric Restriction ◽

Visceral Adipose Tissue ◽

Breast Cancer Survivors ◽

Vigorous Physical Activity ◽

Supervised Exercise ◽

Visceral Adipose ◽

Sedentary Women

Aerobic exercise reduces risk for breast cancer and recurrence and promotes visceral adipose tissue (VAT) loss in obesity. However, few breast cancer survivors achieve recommended levels of moderate to vigorous physical activity (MVPA) without supervision. In a two-cohort study, feasibility of 12 weeks of partially supervised exercise was started concomitantly with caloric restriction and effects on body composition and systemic risk biomarkers were explored. In total, 22 obese postmenopausal sedentary women (including 18 breast cancer survivors) with median age of 60 and BMI of 37 kg/m2 were enrolled. Using personal trainers twice weekly at area YMCAs, MVPA was escalated to ≥200 min/week over 9 weeks. For cohort 2, maintenance of effect was assessed when study provided trainer services were stopped but monitoring, group counseling sessions, and access to the exercise facility were continued. Median post-escalation MVPA was 219 min/week with median 12-week mass and VAT loss of 8 and 19%. MVPA was associated with VAT loss which was associated with improved adiponectin:leptin ratio. In total, 9/11 of cohort-2 women continued the behavioral intervention for another 12 weeks without trainers. High MVPA continued with median 24-week mass and VAT loss of 12 and 29%. This intervention should be further studied in obese sedentary women.

Download Full-text