scholarly journals Individual and combined effects of 5-year exposure to hyperandrogenemia and Western-style diet on metabolism and reproduction in female rhesus macaques

2020 ◽  
Author(s):  
Cecily V Bishop ◽  
Diana Takahashi ◽  
Emily Mishler ◽  
Ov D Slayden ◽  
Charles T Roberts ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Body Fat ◽  
Rhesus Macaques ◽  
Post Partum ◽  
Metabolic Effects ◽  
Metabolic Function ◽  
Female Rhesus ◽  
Female Rhesus Macaques

Abstract STUDY QUESTION What is the impact of prolonged exposure to hyperandrogenemia (T), Western-style diet (WSD) and the combination on metabolic and reproductive function in female rhesus macaques, particularly in the post-partum period? SUMMARY ANSWER Combined T + WSD worsened measures of insulin sensitivity and parameters of cyclicity following prolonged (5 years) exposure, but there was no effect on post-partum metabolic function. WHAT IS KNOWN ALREADY Women with hyperandrogenemia due to polycystic ovary syndrome are at higher risk for gestational diabetes and Type 2 diabetes post-partum, but it is unknown if this is related to hyperandrogenemia. Hyperandrogenemia in the presence of a WSD worsens metabolic function in female nonhuman primates. STUDY DESIGN, SIZE, DURATION Female rhesus macaques began treatment near menarche (roughly 2.5 years of age) consisting of either cholesterol (control; C) or testosterone (T) implants (average serum levels 1.4 ng/ml) and exposure to standard monkey chow or a WSD (15 vs 36% of calories from fat, respectively). The four groups were maintained on treatment for 3 years, underwent a fertility trial in Year 4 and continued with treatments through Year 5. PARTICIPANTS/MATERIALS, SETTING, METHODS Metabolic measurements (glucose tolerance tests and double X-ray absorptiometry scans) were performed yearly, and results from 5 years of treatment are reported for all animals. Animals were bled daily for 30 days at 5 years to capture changes in ovarian cycle hormones, and ultrasound measurements were performed during the early follicular and luteal phase. MAIN RESULTS AND THE ROLE OF CHANCE After 5 years of treatment, WSD exposure moderately increased body weight and body fat, although control animals also had a high body mass index due to ad libitum feeding. Animals in the T + WSD group had increased fasting insulin and insulin secretion during an intravenous glucose tolerance test. WSD exposure also altered ovarian cycles, delaying the time to the E2 surge, decreasing progesterone and anti-Müllerian hormone levels and increasing the number of antral follicles present by ultrasound. Longitudinal assessment of metabolic function for only those animals that became pregnant in Year 4 of treatment revealed no differences in post-partum metabolism between groups, although WSD resulted in overall elevated weights, body fat and measures of insulin resistance. LARGE SCALE DATA None. LIMITATIONS, REASONS FOR CAUTION The small sample size and heterogeneity in metabolic effects observed in the T + WSD group are limitations of the current study, with only a subset of animals in this group showing impaired insulin resistance relative to controls. In addition, obesity in the C group prevented comparisons to lean animals. WIDER IMPLICATIONS OF THE FINDINGS Hyperandrogenemia combined with WSD had a greater impact on insulin sensitivity and ovarian function than either treatment alone. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by NIH grant P50 HD071836 to C.T.R., J.H. and C.T. and P51 OD011092 for support of the Oregon National Primate Research Center. All authors declare no competing interests.

Abstract P250: Insulin Resistance During Pregnancy is Inversely Associated With Gynoid Fat Distribution Postpartum

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Katherine H Ingram ◽  
Roxanna Lopez
Keyword(s):  
Insulin Resistance ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Gestational Weight Gain ◽  
Body Fat ◽  
Visceral Fat ◽  
Post Partum ◽  
Lower Body ◽  
Negatively Associated ◽  
Gestational Weight

An association between abdominal adiposity and insulin resistance is well-established. Recent research indicates that subcutaneous fat accumulation in the lower body may be associated with higher levels of insulin sensitivity. Hypothesis: This pilot study tested the hypothesis that the distribution of body fat in the lower body after pregnancy is negatively associated with gestational insulin resistance. Methods: In 32 nulliparous pregnant women (age 27±4.5, BMI 29.5±7.9, 69% non-hispanic white), the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was computed from fasting glucose and insulin at 24-28 weeks gestation. Body composition was assessed at mid-gestation (18-20 weeks) and at four weeks post-partum. Total body fat was estimated via bioelectrical impedance (InBody 720) and skinfold thicknesses were measured at seven sites. Dual-energy xray absorptiometry (DXA) measures of regional fat (gynoid, visceral, and leg) were obtained post-partum only. Gestational weight gain was monitored by medical records. Partial correlation analyses were controlled for age and race and then analyses were repeated controlling for baseline (mid-gestation) body fat percent. HOMA-IR was log-transformed for normality. Results: HOMA-IR was associated with post-partum body fat ( r =0.45, p < .05) and adiposity in the trunk region ( r =0.58, 0.57 and 0.52 for DXA visceral fat, suprailiac skinfold, and abdominal skinfold, respectively, p < .01), but not with gestational weight gain ( r =.07, p = ns), DXA gynoid region ( r = 0.26, p = ns), or any other leg measure. When analyses were further controlled for baseline body fat, post-partum measures of lower-body adiposity were strongly and negatively correlated with HOMA-IR ( r = -0.66, -0.48, and -0.48 for thigh skinfold, DXA gynoid, and DXA leg, respectively, p < .05 for all). Neither DXA visceral fat ( r = .23; p = ns) nor any other post-partum fat measures were associated with HOMA-IR when controlling for baseline body fat. Conclusions: Gestational insulin resistance was negatively associated with post-partum thigh fat accumulation, independent of overall body fat. These data indicate that insulin sensitivity may be associated with the ability to store fat in the lower body and should warrant further study of subcutaneous leg fat as a metabolically “healthy” storage depot.

scholarly journals Low-calorie sweeteners cause only limited metabolic effects in mice

2020 ◽  
Vol 318 (1) ◽  
pp. R70-R80 ◽  
Author(s):  
John I. Glendinning ◽  
Stephanie Hart ◽  
Hyunseo Lee ◽  
Jennifer Maleh ◽  
Gabriella Ortiz ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Body Fat ◽  
Glucose Solution ◽  
Metabolic Changes ◽  
Metabolic Effects ◽  
Percent Body Fat ◽  
Metabolic Derangement ◽  
Low Calorie ◽  
Glucose Challenge

There are widespread concerns that low-calorie sweeteners (LCSs) cause metabolic derangement. These concerns stem in part from prior studies linking LCS consumption to impaired glucose tolerance in humans and rodents. Here, we examined this linkage in mice. In experiment 1, we provided mice with chow, water, and an LCS-sweetened solution (saccharin, sucralose, or acesulfame K) for 28 days and measured glucose tolerance and body weight across the exposure period. Exposure to the LCS solutions did not impair glucose tolerance or alter weight gain. In experiment 2, we provided mice with chow, water, and a solution containing saccharin, glucose, or a mixture of both for 28 days, and tested for metabolic changes. Exposure to the saccharin solution increased the insulinemic response of mice to the glucose challenge, and exposure to the saccharin + glucose solution increased the rate of glucose uptake during the glucose challenge. However, neither of these test solutions altered glucose tolerance, insulin sensitivity, plasma triglycerides, or percent body fat. In contrast, exposure to the glucose solution increased glucose tolerance, early insulin response, insulin sensitivity, and percent body fat. We conclude that whereas the LCS-containing solutions induced a few metabolic changes, they were modest compared with those induced by the glucose solution.

scholarly journals Intrahepatic lipid, not visceral or muscle fat, is correlated with insulin resistance in older, female rhesus macaques

Obesity ◽  
2013 ◽  
Vol 21 (10) ◽  
pp. 2021-2028 ◽  
Author(s):  
Michael P. Chu ◽  
Bethany J. Klopfenstein ◽  
Christine M. Krisky ◽  
Henryk F. Urbanski ◽  
William D. Rooney ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Rhesus Macaques ◽  
Female Rhesus ◽  
Intrahepatic Lipid ◽  
Female Rhesus Macaques

scholarly journals Effect of Housing Conditions on Cortisol and Body Fat Levels in Female Rhesus Macaques

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 744
Author(s):  
Dian G. M. Zijlmans ◽  
Lisette Meijer ◽  
Marit K. Vernes ◽  
Jacqueline A. M. Wubben ◽  
Linda Hofman ◽  
...  
Keyword(s):  
Body Fat ◽  
Individual Variation ◽  
Rhesus Macaques ◽  
Dominance Rank ◽  
Individual Characteristics ◽  
Study Results ◽  
Female Rhesus ◽  
Cortisol Levels ◽  
Female Rhesus Macaques

Macaques are among the most commonly used non-human primates in biomedical research. They are highly social animals, yet biomedical studies often require group-living animals to be pair-housed in a controlled environment. A change in environment causes only short-term stress in adapting individuals, while non-adapting animals may experience long-term stress that can adversely affect study results. Individuals likely differ in their ability to adapt depending on individual characteristics. Changes in cortisol and body fat levels may reflect these different individual responses. Here, we investigate the long-term effect of a change from group- to pair-housing on cortisol and body fat levels in 32 female rhesus macaques, exploring whether age, dominance rank, original cortisol, and body fat levels are related to long-term stress in pair-housing. Hair samples were analyzed for cortisol levels, while anthropometric measurements and computed tomography were performed to quantify body fat. Monkeys served as their own control with a 7.5-month period between the measurements. Cortisol levels increased, while average body fat levels did not differ when individuals were moved from group- to pair-housing. Cortisol and body fat levels were not significantly correlated. Changes in cortisol were independent of age and dominance rank, whereas individual variation in body fat alterations was related to the group-housed body fat level and dominance rank. Although this study did not identify individual characteristics related to long-term stress in pair-housing, the individual variation confirms that some individuals are more resilient to change than others and provides possibilities for future refinement studies.

scholarly journals Beneficial Effect of Diazoxide in Obese Hyperinsulinemic Adults1

1998 ◽  
Vol 83 (6) ◽  
pp. 1911-1915 ◽  
Author(s):  
Ramin Alemzadeh ◽  
Gina Langley ◽  
Lori Upchurch ◽  
Pam Smith ◽  
Alfred E. Slonim
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Body Fat ◽  
Therapeutic Potential ◽  
Controlled Trial ◽  
Insulin Response ◽  
Tolerance Test ◽  
Fat Free Mass ◽  
Zucker Rats ◽  
Significant Difference

Hyperinsulinemia, insulin resistance, and increased adipose tissue are hallmarks of the obesity state in both humans and experimental animals. The role of hyperinsulinemia as a possible preceding event in the development of obesity has been proposed. We previously demonstrated that administration of diazoxide (DZ), an inhibitor of insulin secretion, to obese hyperinsulinemic Zucker rats resulted in less weight gain, enhanced insulin sensitivity, and improved glucose tolerance. Assuming that hyperinsulinemia plays a major role in the development of human obesity, then its reversal should have therapeutic potential. To test this hypothesis, we conducted a randomized placebo-controlled trial in 24 hyperinsulinemic adults [body mass index (BMI) &gt; 30 kg/m2]. All subjects were placed on a low-calorie (1260 for females and 1570 for males) Optifast (Sandoz, Minneapolis, MN) diet. After an initial 1-week lead-in period, 12 subjects (mean ± se for age and BMI, 31 ± 1 and 40 ± 2, respectively) received DZ (2 mg/kg BW·day; maximum, 200 mg/day, divided into 3 doses) for 8 weeks; and 12 subjects (mean± se for age and BMI, 28 ± 1 and 43 ± 1, respectively) received placebo. Compared with the placebo group, DZ subjects had greater weight loss (9.5 ± 0.69% vs. 4.6 ± 0.61%, P &lt; 0.001), greater decrease in body fat (P &lt; 0.01), greater increase in fat-free mass to body fat ratio (P &lt; 0.01), and greater attenuation of acute insulin response to glucose (P &lt; 0.01). However, there was no significant difference in insulin sensitivity and glucose effectiveness, as determined by the insulin-modified iv glucose tolerance test (Bergman’s minimal model) and no significant difference in glycohemoglobin values. Conclusion: 8 weeks treatment with DZ had a significant antiobesity effect in hyperinsulinemic obese adults without inducing hyperglycemia.

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