Obesity, adipokines and neuroinflammation

Aguilar‐Valles, Argel; Inoue, Wataru; Rummel, Christoph; Luheshi, Giamal N.

doi:10.1016/j.neuropharm.2014.12.023

Cited by 138 publications

(143 citation statements)

References 216 publications

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“…There might be decreased availability or binding‐affinity of CBG, the primary plasma binding protein for cortisol, in these endocrine diseases. Both obesity and aging also appear to be associated with a chronic low‐grade inflammatory state in both people and animals, characterized by increased expression or activity of adipose‐derived proinflammatory mediators such as interleukin‐6 (IL‐6) and leptin48, 49, 50, 51, 52, 53, 54, 55 In sepsis and other systemic inflammatory states, inflammatory mediators such as IL‐6 and neutrophil elastase respectively inhibit hepatic production of CBG and perpetuate the cleavage of high‐binding affinity CBG into a low‐affinity confirmation 56, 57, 58. Thus, both mechanisms could lead to increases in FCF.…”

Section: Discussionmentioning

confidence: 99%

“…This is mostly likely because of obesity‐related increases in HPA axis activity or 11‐β‐HSD1 expression,48, 49, 50, 51, 52, 53, 54, 55 as discussed above in relation to FCF in animals with endocrine disease. It is possible that an increase in total circulating cortisol, which has global anti‐inflammatory effects that include inhibition of pro‐inflammatory mediator production and leukocyte migration into tissues,7, 20, 63 is actually an appropriate response to an obesity‐induced inflammatory state.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Age, Season, Body Condition, and Endocrine Status on Serum Free Cortisol Fraction and Insulin Concentration in Horses

Hart

Wochele

Norton

et al. 2016

Veterinary Internal Medicne

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BackgroundIncreased free cortisol fraction is associated with insulin dysregulation (ID) in people with Metabolic Syndrome and Cushing's Disease. Free cortisol has not been investigated in equine endocrine disorders.Hypotheses(1) In healthy horses, sex, age, body condition score (BCS), and season impact free cortisol; (2) free cortisol is increased in horses with Pituitary Pars Intermedia Dysfunction (PPID) or Equine Metabolic Syndrome (EMS).AnimalsFifty‐seven healthy horses; 40 horses and ponies with PPID (n = 20) or EMS (n = 20).MethodsProspective study. Serum collected seasonally from healthy animals and archived serum from PPID and EMS animals was analyzed for insulin, total and free cortisol concentrations, and free cortisol fraction (FCF). Linear mixed models were used to determine effects of age, sex, season, and BCS on hormones in controls. Hormone measurements were compared between disease groups and age‐ and season‐matched controls with t‐tests. EMS and hyperinsulinemic PPID animals were combined in an ID (hyperinsulinemia) group.ResultsFree cortisol concentrations were increased in overweight/obese controls (0.3 ± 0.1 μg/dL) compared to lean controls (0.2 ± 0.1 μg/dL; P = .017). Mean FCF was significantly higher in animals with PPID (8.8 ± 5.8 μg/dL, P = .005) or ID (8.8 ± 10.2 μg/dL, P = .039) than controls (5.0 ± 0.9 μg/dL), but total cortisol concentrations were similar (P ≥ .350) (PPID: 4.2 ± 4.3 μg/dL; ID: 5.0 ± 4.5 μg/dL; controls: 4.6 ± 1.7 and 5.1 ± 2.1 μg/dL).Conclusions and Clinical ImportanceIncreased FCF is associated with obesity in healthy horses and with ID (hyperinsulinemia) in horses and ponies with endocrine disease. Decreased plasma cortisol‐binding capacity could be a component of these endocrine disorders in horses.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of Age, Season, Body Condition, and Endocrine Status on Serum Free Cortisol Fraction and Insulin Concentration in Horses

Hart

Wochele

Norton

et al. 2016

Veterinary Internal Medicne

View full text Add to dashboard Cite

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“…On the other hand, it has been proposed that circulating inflammatory mediators manufactured and released by white adipose tissue are important in the development of steatosis and subsequent progression of liver disease and insulin resistance [233][234][235]. In particular, the adipokine resistin, which is secreted from adipocytes in rodents influences adipogenesis, increases triglyceride synthesis and suppress mitochondrial fatty acid ␤-oxidation, resulting in the accumulation of intracellular lipids in adipocytes [236,237].…”

Section: Antisteatosic Properties Of Eamentioning

confidence: 99%

Ellagic acid: Pharmacological activities and molecular mechanisms involved in liver protection

García-Niño

Zazueta

2015

Pharmacological Research

201

118

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“…For example, since obesity is associated with an up-regulation of inflammatory cytokines [218] , and chronic low grade systemic inflammation has been shown to contributed to age-related muscle wasting [219] , it is possible that ADT-induced increases in fat mass and size may further exacerbate the loss in muscle mass and size in men with PCa undergoing this treatment. Thus, possessing a number of ADT-induced adverse effects may predispose these men to a greater risk of various clinical implications and further research is required to progress this understanding.…”

Section: The Clinical Implications Of Androgen Deprivation Therapy-rementioning

confidence: 99%

Muscle, fat and performance during androgen deprivation for prostate cancer

Owen¹

2018

Preprint

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Introduction: Prostate cancer (PCa) is one of the most frequently diagnosed male cancers worldwide. One treatment, androgen deprivation therapy (ADT), is often accompanied with a myriad of adverse effects, including those that negatively impact muscle, fat and performance outcomes. Therefore, ADT-treated men may be living longer, but are at risk of both age- and treatment-related complications. The overall aim of this thesis was to quantify outcomes of muscle, fat and performance in men treated with ADT when compared to PCa (men diagnosed with PCa, not treated with ADT) and healthy controls (men not diagnosed with PCa), and assess the feasibility of implementing a multi-component exercise program combined with protein, calcium and vitamin D supplementation (Ex+ProCaD) compared to usual care in ADT-treated men. Methods: This thesis presents two studies that form part of a larger 52-week randomised controlled trial (RCT), which examined the efficacy of Ex+ProCaD compared to usual care in men treated with ADT for PCa. The first study presented was a nested cross-sectional study performed parallel to the baseline assessment of the RCT and examined differences in muscle, fat and performance outcomes between men treated with ADT when compared to PCa and healthy controls. The second study presented examined the feasibility of implementing the first 26 weeks of the RCT. Results: The cross-sectional study showed that height, weight, body mass index and diet were similar between the three groups, but ADT-treated men were four years older and tended to be less physically active (23-30%; P=0.054). After adjusting for age and physical activity, total body fat mass was 3.3-5.0 kg (P < 0.05) greater in men treated with ADT compared to PCa controls, but there was no difference in total body and regional lean mass. When adiposity was considered, ADT-treated men had 10-12% (P < 0.05) lower appendicular lean mass adjusted for body mass index and 5.6-6.4% (P < 0.05) lower forearm percent muscle cross-sectional area compared to controls. Absolute muscle strength was similar between groups, but when expressed relative to body weight, men treated with ADT had 13-21% (P < 0.05) lower muscle strength compared to controls. Whilst only two ADT-treated men had sarcopenia, these men had a higher proportion (P < 0.001) of pre-sarcopenia when appendicular lean mass was adjusted for body mass index (42%) compared to PCa (15%) and healthy (7%) controls. Men treated with ADT had 15-36% (P < 0.05) greater storage of fat within subcutaneous depots when compared to controls, whereas visceral and intermuscular fat was similar. The majority of subcutaneous fat depots (excluding android region) were shown to be positively associated with ADT duration (P < 0.05). Forearm muscle density was shown to negatively correlate with ADT duration (P < 0.05). The RCT had a high participant retention rate (96%). Adherence was high for the supplement (mean, 92-93%) and modest for the exercise program (mean, 60%). A relatively high proportion (81%) of men in the intervention group reported an adverse event, although only 16% were confirmed to be related to the intervention and the vast majority (97%) were determined to be mild or moderate in terms of severity. Across the ten separate recruitment pathways considered, clinician referral (43%) and PCa support groups (29%) yielded the greatest proportion of enrolled participants. A total of 149 potential participants were screened, which resulted in 42 participants at the time of write up for this thesis. Among the first 28 participants to complete the 26-week intervention, 21-50% were unable to complete at least one measure of muscle strength due to pre-existing comorbidities. Data from the initial 28 participants tended to show that when compared to usual care, Ex+ProCaD led to net improvements in lean mass (0.2-1.4 kg), fat mass (-0.1 to -0.9 kg), muscle strength (8.0-19%), functional muscle power (8.6%) and functional capacity (12-14%). Conclusions: The following key themes emerged from this thesis and may be used to guide clinical practice guidelines and future research: 1) Men treated with ADT for PCa had greater amounts of fat when compared to non-ADT counterparts, 2) Current definitions of sarcopenia and sarcopenic obesity were limited in men treated with ADT for PCa, 3) The greater amounts of fat observed in men treated with ADT for PCa tended to be stored in subcutaneous depots and supersede age-related plateaus/losses, 4) The recruitment of men treated with ADT for PCa into a lifestyle intervention was challenging, and 5) Men treated with ADT for PCa tended to respond positively to a multi-modal exercise training combined with multi-nutrient supplementation.

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Obesity, adipokines and neuroinflammation

Cited by 138 publications

References 216 publications

Effect of Age, Season, Body Condition, and Endocrine Status on Serum Free Cortisol Fraction and Insulin Concentration in Horses

Effect of Age, Season, Body Condition, and Endocrine Status on Serum Free Cortisol Fraction and Insulin Concentration in Horses

Ellagic acid: Pharmacological activities and molecular mechanisms involved in liver protection

Muscle, fat and performance during androgen deprivation for prostate cancer

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