Combined androgen excess and Western-style diet accelerates adipose tissue dysfunction in young adult, female nonhuman primates

Varlamov, Oleg; Bishop, Cecily V.; Handu, Mithila; Takahashi, Diana; Srinivasan, Sathya; White, Ashley E.; Roberts, Charles T.

doi:10.1093/humrep/dex244

Cited by 32 publications

(52 citation statements)

References 73 publications

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“…Hyperandrogenemia was also associated with an altered pattern of physical activity, with androgen-treated females showing a delay in the usual puberty-associated decline in activity, followed by a more rapid decline later in the study, corresponding to the period when weight gain was observed. Similar to the findings in hyperandrogenized prepubertal animals described above, peripubertal treatment with androgens resulted in impaired lipolysis ex vivo [73]. Basal lipolytic activity was significantly reduced in OM and SC-WAT, while the β-adrenergic lipolytic response was significantly decreased only in SC-WAT (Figure 2).…”

Section: Effects Of Androgens On Female Nhp Metabolismsupporting

confidence: 83%

“…Adipocytes also appeared to be affected by the combined treatment, with larger visceral adipocytes and increased fatty acid uptake in visceral WAT in the T+WSD group compared to all other groups. Female rhesus macaques exposed to hyperandrogenemia and WSD exhibited an increase in the average size of visceral adipocytes that correlated with greater insulin resistance compared to animals treated with T or WSD alone [72]; [73] (Figure 3). As noted above, certain metabolic effects were often statistically identified as being driven by either diet or androgen in isolation; however, the group receiving both androgens and WSD was often significantly different from all other groups, indicating a more extreme metabolic phenotype when both conditions were present.…”

Section: Interactions Between Androgens and Dietmentioning

confidence: 99%

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Sex Differences in Androgen Regulation of Metabolism in Nonhuman Primates

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Abbott

Roberts

et al. 2017

Sex and Gender Factors Affecting Metabolic Homeostasis, Diabetes and Obesity

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The in-depth characterization of sex differences relevant to human physiology requires the judicious use of a variety of animal models and human clinical data. Nonhuman primates (NHPs) represent an important experimental system that bridges rodent studies and clinical investigations. NHP studies have been especially useful in understanding the role of sex hormones in development and metabolism and also allow the elucidation of the effects of pertinent dietary influences on physiology pertinent to disease states such as obesity and diabetes. This chapter summarizes the current state of our understanding of androgen effects on male and female NHP metabolism relevant to hypogonadism in human males and polycystic ovary syndrome in human females, as well as the interaction between altered androgen levels and dietary restriction and excess, in particular the western-style diet that underlies significant human pathophysiology.

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Section: Effects Of Androgens On Female Nhp Metabolismsupporting

confidence: 83%

Section: Interactions Between Androgens and Dietmentioning

confidence: 99%

Sex Differences in Androgen Regulation of Metabolism in Nonhuman Primates

True

Abbott

Roberts

et al. 2017

Sex and Gender Factors Affecting Metabolic Homeostasis, Diabetes and Obesity

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“…According reported methods (Murugesan et al, 2015; Varlamov et al, 2017), after fixation and dehydration, samples of different intestinal segments and abdominal tissue were embedded (EG1150H, LEIC, Germany) in paraffin wax, sliced (rotary microtome, RM2016, LEIC, Germany) and stained with hematoxylin and eosin in preparation for examination by microscope (S4E, LEIC, Germany), and image analyzer (Image-ProPlus 6.0). For each intestinal sample, 5 villus were selected for Villus height (VH), crypt depth (CD), mucosal thickness determination.…”

Section: Methodsmentioning

confidence: 99%

Associations of Gut Microbiota With Heat Stress-Induced Changes of Growth, Fat Deposition, Intestinal Morphology, and Antioxidant Capacity in Ducks

Pan

et al. 2019

Front. Microbiol.

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Accumulating evidence has revealed the dysbiosis of gut/fecal microbiota induced by heat stress (HS) in mammals and poultry. However, the effects of HS on microbiota communities in different intestinal segments of Cherry-Valley ducks (a widely used meat-type breed) and their potential associations with growth performances, fat deposition, intestinal morphology, and antioxidant capacity have not been well evaluated yet. In this study, room temperature (RT) of 25°C was considered as control, and RT at 32°C for 8 h per day was set as the HS treatment. After 3 weeks, the intestinal contents of jejunum, ileum, and cecum were harvested to investigate the microbiota composition variations by 16S ribosomal RNA amplicon sequencing. And the weight gain, adipose indices, intestinal morphology, and a certain number of serum biochemical parameters were also measured and analyzed. The results showed the microbial species at different levels differentially enriched in duck jejunum and cecum under HS, while no significant data were observed in ileum. HS also caused the intestinal morphological changes (villus height and the ratio of villus height to crypt depth) and the reductions of growth speed (daily gain), levels of serum triglyceride (TG) and total cholesterol, and antioxidant activity (higher malondialdehyde (MDA) content and lower total antioxidant). The higher abdominal fat content and serum glucose level were also observed in HS ducks. The Spearman correlation analysis indicated that in jejunum the phyla Firmicutes and Proteobacteria were associated with average daily gain, feed/gain, serum TG and MDA levels, and villus height/crypt depth ( P < 0.05). The phylum Firmicutes and genus Acinetobacter were significantly associated with fat deposition and serum glucose level ( P < 0.05). The genus Lactobacillus was positively associated with serum total antioxidant ( P < 0.05), while some other microbial species were found negatively associated, including order Pseudomonadales , genera Acinetobacter , and unidentified_Mitochondria . However, no significant correlations were observed in cecum. These findings imply the potential roles of duck gut microbiota in the intestinal injuries, fat deposition, and reductions of growth speed and antioxidant capacity caused by HS, although the molecular mechanisms requires further investigation.

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“…In summary, the present study advances our understanding of the functional and transcriptional response in SC-WAT associated with dynamic changes in fat mass in response to diet-induced obesity and weight loss and expands our previous studies in NHPs [17,18,20,[64][65][66]. Our study has several limitations.…”

Section: Discussionmentioning

confidence: 64%

“…Free fatty acid (FFA) uptake, adipocyte size and lipolysis was conducted as previously described [17,[20][21][22]. For the lipolysis assay,~200-mg SC-WAT explants were placed in M199 media (General Electric Company, Boston, MA, USA) at room temperature and transported to the laboratory.…”

Section: Cell-based Assaysmentioning

confidence: 99%

Short-Term Caloric Restriction Attenuates Obesity-Induced Pro-inflammatory Response in Male Rhesus Macaques

et al. 2020

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White adipose tissue (WAT) hypertrophy is an essential hallmark of obesity and is associated with the activation of resident immune cells. While the benefits of caloric restriction (CR) on health span are generally accepted, its effects on WAT physiology are not well understood. We previously demonstrated that short-term CR reverses obesity in male rhesus macaques exposed to a high-fat Western-style diet (WSD). Here, we analyzed subcutaneous WAT biopsies collected from this cohort of animals before and after WSD and following CR. This analysis showed that WSD induced adipocyte hypertrophy and inhibited β-adrenergic-simulated lipolysis. CR reversed adipocyte hypertrophy, but WAT remained insensitive to β-adrenergic agonist stimulation. Whole-genome transcriptional analysis revealed that β3-adrenergic receptor and de novo lipogenesis genes were downregulated by WSD and remained downregulated after CR. In contrast, WSD-induced pro-inflammatory gene expression was effectively reversed by CR. Furthermore, peripheral blood monocytes isolated during the CR period exhibited a significant reduction in the production of pro-inflammatory cytokines compared to those obtained after WSD. Collectively, this study demonstrates that short-term CR eliminates an obesity-induced pro-inflammatory response in WAT and peripheral monocytes.

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Combined androgen excess and Western-style diet accelerates adipose tissue dysfunction in young adult, female nonhuman primates

Cited by 32 publications

References 73 publications

Sex Differences in Androgen Regulation of Metabolism in Nonhuman Primates

Sex Differences in Androgen Regulation of Metabolism in Nonhuman Primates

Associations of Gut Microbiota With Heat Stress-Induced Changes of Growth, Fat Deposition, Intestinal Morphology, and Antioxidant Capacity in Ducks

Short-Term Caloric Restriction Attenuates Obesity-Induced Pro-inflammatory Response in Male Rhesus Macaques

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