scholarly journals Mass Recovery following Caloric Restriction Reverses Lipolysis and Proteolysis, but not Gluconeogenesis, in Insulin Resistant OLETF Rats

2021 ◽  
Author(s):  
Manuel Alejandro Cornejo ◽  
Jaapna Dhillon ◽  
Akira Nishiyama ◽  
Daisuke Nakano ◽  
Rudy M. Ortiz

Caloric restriction (CR) is one of the most important behavioral interventions to reduce excessive abdominal adiposity, which is a risk factor for the development of insulin resistance. Previous metabolomics studies have characterized substrate metabolism during healthy conditions; however, the effects of CR and subsequent mass recovery on shifts in substrate metabolism during insulin resistance (IR) have not been widely investigated. To assess the effects of acute CR and the subsequent mass recovery on shifts in substrate metabolism, a cohort of 15-week old Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats were calorie restricted (CR: 50% × 10 days) with or without partial body mass recovery (PR; 73% x 7 days), along with their respective ad libitum controls. End-of-study plasma samples were analyzed for primary carbon metabolites by gas chromatography (GC) time-of-flight (TOF) mass spectrometry (MS) data acquisition. Data analysis included PCA, Pearson correlation vs previously reported variables (adipose and body masses, and insulin resistance index, IRI), and metabolomics maps (MetaMapp) generated for the most significant group comparisons. All treatments elicited a significant group differentiation in at least one principal component. CR improved TCA cycle in OLETF, and increased lipolysis and proteolysis. These changes were reversed after PR except for gluconeogenesis. Plasma lipid concentrations were inversely correlated to IRI in LETO, but not OLETF. These shifts in substrate metabolism suggest that the CR-induced decreases in adipose may not be sufficient to more permanently alter substrate metabolism to improve IR status during metabolic syndrome.

2007 ◽  
Vol 127 (11) ◽  
pp. 1877-1882 ◽  
Author(s):  
Masataka NOMURA ◽  
Naomi MARUO ◽  
Yoshito ZAMAMI ◽  
Shingo TAKATORI ◽  
Shima DOI ◽  
...  

2011 ◽  
Vol 300 (5) ◽  
pp. G874-G883 ◽  
Author(s):  
R. Scott Rector ◽  
Grace M. Uptergrove ◽  
E. Matthew Morris ◽  
Sarah J. Borengasser ◽  
M. Harold Laughlin ◽  
...  

The maintenance of normal body weight either through dietary modification or being habitually more physically active is associated with reduced incidence of nonalcoholic fatty liver disease (NAFLD). However, the means by which weight gain is prevented and potential mechanisms activated remain largely unstudied. Here, we sought to determine the effects of obesity prevention by daily exercise vs. caloric restriction on NAFLD in the hyperphagic, Otsuka Long-Evans Tokushima Fatty (OLETF) rat. At 4 wk of age, male OLETF rats ( n = 7–8/group) were randomized to groups of ad libitum fed, sedentary (OLETF-SED), voluntary wheel running exercise (OLETF-EX), or caloric restriction (OLETF-CR; 70% of SED) until 40 wk of age. Nonhyperphagic, control strain Long-Evans Tokushima Otsuka (LETO) rats were kept in sedentary cage conditions for the duration of the study (LETO-SED). Both daily exercise and caloric restriction prevented obesity and the development of type 2 diabetes observed in the OLETF-SED rats, with glucose tolerance during a glucose tolerance test improved to a greater extent in the OLETF-EX animals (30–50% lower glucose and insulin areas under the curve, P < 0.05). Both daily exercise and caloric restriction also prevented excess hepatic triglyceride and diacylglycerol accumulation ( P < 0.001), hepatocyte ballooning and nuclear displacement, and the increased perivenular fibrosis and collagen deposition that occurred in the obese OLETF-SED animals. However, despite similar hepatic phenotypes, OLETF-EX rats also exhibited increased hepatic mitochondrial fatty acid oxidation, enhanced oxidative enzyme function and protein content, and further suppression of hepatic de novo lipogenesis proteins compared with OLETF-CR. Prevention of obesity by either daily exercise or caloric restriction attenuates NAFLD development in OLETF rats. However, daily exercise may offer additional health benefits on glucose homeostasis and hepatic mitochondrial function compared with restricted diet alone.


2012 ◽  
Vol 37 (6) ◽  
pp. 1054-1062 ◽  
Author(s):  
Justin A. Fletcher ◽  
Grace M. Meers ◽  
M. Harold Laughlin ◽  
Jamal A. Ibdah ◽  
John P. Thyfault ◽  
...  

Chronic treatment with fibroblast growth factor 21 (FGF-21) favorably improves obesity and nonalcoholic fatty liver disease (NAFLD) outcomes; however, FGF-21 expression is paradoxically elevated in obese conditions. Here, we sought to determine the effects of obesity prevention by daily exercise (EX) vs. caloric restriction (CR) on hepatic FGF-21 in the hyperphagic, Otsuka Long-Evans Tokushima Fatty (OLETF) rat. Four-week-old male OLETF rats were randomized into groups (n = 7–8 per group) of ad libitum fed, sedentary (OLETF-SED), voluntary wheel running exercise (OLETF-EX), or CR (OLETF-CR; 70% of SED) until 40 weeks of age. Nonhyperphagic, Long-Evans Tokushima Otsuka (LETO-SED) rats served as controls. Both daily EX and CR prevented obesity and NAFLD development observed in the OLETF-SED animals. This was associated with significantly (p < 0.01) lower serum FGF-21 (~80% lower) and hepatic FGF-21 mRNA expression (~65% lower) in the OLETF-EX and OLETF-CR rats compared with the OLETF-SED rats. However, hepatic FGF-21 protein content was reduced to the greatest extent in the OLETF-EX animals (50% of OLETF-SED) and did not differ between the OLETF-SED and OLETF-CR rats. Hepatic FGF-21 signaling mediators — hepatic FGF-21 receptor 2 (FGFR2, mRNA expression), hepatic FGF-21 receptor substrate 2 (FRS2, protein content), and co-receptor β-Klotho (protein content) — were all elevated (60%–100%, ~40%, and +30%–50%, respectively) in the OLETF-EX and OLETF-CR animals compared with the OLETF-SED animals. Daily exercise and caloric restriction modulate hepatic FGF-21 and its primary signaling mediators in the hyperphagic OLETF rat. Enhanced metabolic action of FGF-21 may partially explain the benefits of exercise and caloric restriction on NAFLD outcomes.


2010 ◽  
Vol 298 (6) ◽  
pp. E1179-E1187 ◽  
Author(s):  
R. Scott Rector ◽  
Grace M. Uptergrove ◽  
Sarah J. Borengasser ◽  
Catherine R. Mikus ◽  
E. Matthew Morris ◽  
...  

The temporal changes in skeletal muscle mitochondrial content and lipid metabolism that precede type 2 diabetes are largely unknown. Here we examined skeletal muscle mitochondrial fatty acid oxidation (MitoFAOX) and markers of mitochondrial gene expression and protein content in sedentary 20- and 40-wk-old hyperphagic, obese Otsuka Long-Evans Tokushima fatty (OLETF-SED) rats. Changes in OLETF-SED rats were compared with two groups of rats who maintained insulin sensitivity: age-matched OLETF rats given access to voluntary running wheels (OLETF-EX) and sedentary, nonobese Long-Evans Tokushima Otsuka (LETO-SED) rats. As expected, glucose tolerance tests revealed insulin resistance at 20 wk that progressed to type 2 diabetes at 40 wk in the OLETF-SED, whereas both the OLETF-EX and LETO-SED maintained whole body insulin sensitivity. At 40 wk, complete MitoFAOX (to CO2), β-hydroxyacyl-CoA dehydrogenase activity, and citrate synthase activity did not differ between OLETF-SED and LETO-SED but were significantly ( P < 0.05) higher in OLETF-EX compared with OLETF-SED rats. Genes controlling skeletal muscle MitoFAOX (PGC-1α, PPARδ, mtTFA, cytochrome c) were not different between OLETF-SED and LETO-SED at any age. Compared with the OLETF-SED, the OLETF-EX rats had significantly ( P < 0.05) higher skeletal muscle PGC-1α, cytochrome c, and mtTFA mRNA levels at 20 and 40 wk and PPARδ at 40 wk; however, protein content for each of these markers did not differ between groups at 40 wk. Limited changes in skeletal muscle mitochondria were observed during the transition from insulin resistance to type 2 diabetes in the hyperphagic OLETF rat. However, diabetes prevention through increased physical activity appears to be mediated in part through maintenance of skeletal muscle mitochondrial function.


2012 ◽  
Vol 44 (11) ◽  
pp. 665 ◽  
Author(s):  
Kyoung Soo Kim ◽  
Da Hee Oh ◽  
Jung Yeon Kim ◽  
Bong Gn Lee ◽  
Jeong Soon You ◽  
...  

2010 ◽  
Vol 130 (6) ◽  
pp. 833-840 ◽  
Author(s):  
Yoshito ZAMAMI ◽  
Hiroki FUJIWARA ◽  
Miho HOSODA ◽  
Hayato HINO ◽  
Kazuhiro HIRAI ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
María Isabel Iñiguez-Luna ◽  
Jorge Cadena-Iñiguez ◽  
Ramón Marcos Soto-Hernández ◽  
Francisco Javier Morales-Flores ◽  
Moisés Cortes-Cruz ◽  
...  

AbstractBioprospecting identifies new sources of compounds with actual or potential economic value that come from biodiversity. An analysis was performed regarding bioprospecting purposes in ten genotypes of Sechium spp., through a meta-analysis of 20 information sources considering different variables: five morphological, 19 biochemical, anti-proliferative activity of extracts on five malignant cell lines, and 188 polymorphic bands of amplified fragment length polymorphisms, were used in order to identify the most relevant variables for the design of genetic interbreeding. Significant relationships between morphological and biochemical characters and anti-proliferative activity in cell lines were obtained, with five principal components for principal component analysis (SAS/ETS); variables were identified with a statistical significance (< 0.7 and Pearson values ≥ 0.7), with 80.81% of the accumulation of genetic variation and 110 genetic bands. Thirty-nine (39) variables were recovered using NTSYSpc software where 30 showed a Pearson correlation (> 0.5) and nine variables (< 0.05), Finally, using a cladistics analysis approach highlighted 65 genetic bands, in addition to color of the fruit, presence of thorns, bitter flavor, piriform and oblong shape, and also content of chlorophylls a and b, presence of cucurbitacins, and the IC50 effect of chayote extracts on the four cell lines.


2021 ◽  
Vol 13 (12) ◽  
pp. 6910
Author(s):  
Adil Dilawar ◽  
Baozhang Chen ◽  
Arfan Arshad ◽  
Lifeng Guo ◽  
Muhammad Irfan Ehsan ◽  
...  

Here, we provided a comprehensive analysis of long-term drought and climate extreme patterns in the agro ecological zones (AEZs) of Pakistan during 1980–2019. Drought trends were investigated using the standardized precipitation evapotranspiration index (SPEI) at various timescales (SPEI-1, SPEI-3, SPEI-6, and SPEI-12). The results showed that droughts (seasonal and annual) were more persistent and severe in the southern, southwestern, southeastern, and central parts of the region. Drought exacerbated with slopes of −0.02, −0.07, −0.08, −0.01, and −0.02 per year. Drought prevailed in all AEZs in the spring season. The majority of AEZs in Pakistan’s southern, middle, and southwestern regions had experienced substantial warming. The mean annual temperature minimum (Tmin) increased faster than the mean annual temperature maximum (Tmax) in all zones. Precipitation decreased in the southern, northern, central, and southwestern parts of the region. Principal component analysis (PCA) revealed a robust increase in temperature extremes with a variance of 76% and a decrease in precipitation extremes with a variance of 91% in the region. Temperature and precipitation extremes indices had a strong Pearson correlation with drought events. Higher temperatures resulted in extreme drought (dry conditions), while higher precipitation levels resulted in wetting conditions (no drought) in different AEZs. In most AEZs, drought occurrences were more responsive to precipitation. The current findings are helpful for climate mitigation strategies and specific zonal efforts are needed to alleviate the environmental and societal impacts of drought.


Medicina ◽  
2021 ◽  
Vol 57 (7) ◽  
pp. 668
Author(s):  
Jung-Yup Lee ◽  
Chan-Won Kim ◽  
Kyung-Chul Lee ◽  
Jae-Hyuk Lee ◽  
Sung-Hun Kang ◽  
...  

Background and objectives: Obstructive sleep apnea (OSA) is closely associated with insulin resistance (IR) and is an independent risk factor for incident type 2 diabetes mellitus (T2DM). Most studies evaluate the correlation between OSA and IR in only obese or T2DM patients. Therefore, we tried to investigate the effect of OSA on metabolic syndrome and IR in the general healthy male population. Materials and Methods: 184 subjects who visited a preventive health examination program were recruited for this study. All subjects received overnight polysomnography by a portable device (Watch-PAT 200). We examined several metabolic parameters and a homeostasis model of assessment for insulin resistance index (HOMA-IR). The subjects were divided into three groups by AHI (Apnea-hyponea index): normal group (AHI < 5), mild OSA group (5 ≤ AHI < 15), and moderate-severe OSA group (AHI ≥ 15). They were also divided into two groups according to minimum oxygen saturation: low group, Min-SpO2 < 88%; and high group, Min-SpO2 ≥ 88%. Results: Parameters of metabolic syndrome, including waist circumference, systolic and diastolic blood pressure, triglyceride, and high-density lipoprotein cholesterol showed significant differences among the AHI groups. Furthermore, HOMA-IR showed significant differences among the AHI groups. Those parameters, including metabolic syndrome and HOMA-IR, also showed differences between Min-SpO2 groups. Conclusions: In summary, this study helps confirm that AHI is associated with HOMA-IR in the general male population. Furthermore, the severity of AHI correlated with the parameters of metabolic syndrome. Therefore, AHI might be an indicator for evaluating both T2DM and metabolic syndrome, even in the general male population.


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