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

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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Short Term Glucagon‐Like Peptide‐1 Receptor Agonist Therapy Does Not Influence Hepatic De Novo Lipogenesis in Polycystic Ovary Syndrome

The FASEB Journal ◽

10.1096/fasebj.2021.35.s1.01661 ◽

2021 ◽

Vol 35 (S1) ◽

Author(s):

Jacob Stuppy ◽

Cameron Severn ◽

Elizabeth Parks ◽

Robert Wolfe ◽

Anne‐Marie Carreau ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Receptor Agonist ◽

De Novo ◽

Polycystic Ovary ◽

De Novo Lipogenesis ◽

Agonist Therapy ◽

Short Term ◽

Ovary Syndrome ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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Combining metformin therapy with caloric restriction for the management of type 2 diabetes and nonalcoholic fatty liver disease in obese rats

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2015-0236 ◽

2015 ◽

Vol 40 (10) ◽

pp. 1038-1047 ◽

Cited By ~ 23

Author(s):

Melissa A. Linden ◽

Kristi T. Lopez ◽

Justin A. Fletcher ◽

E. Matthew Morris ◽

Grace M. Meers ◽

...

Keyword(s):

Type 2 Diabetes ◽

Weight Loss ◽

Liver Disease ◽

Caloric Restriction ◽

Fatty Liver Disease ◽

De Novo ◽

De Novo Lipogenesis ◽

Nonalcoholic Fatty Liver ◽

Oletf Rats

Weight loss is recommended for patients with nonalcoholic fatty liver disease (NAFLD), while metformin may lower liver enzymes in type 2 diabetics. Yet, the efficacy of the combination of weight loss and metformin in the treatment of NAFLD is unclear. We assessed the effects of metformin, caloric restriction, and their combination on NAFLD in diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Male OLETF rats (age 20 weeks; n = 6–8 per group) were fed ad libitum (AL), given metformin (300 mg·kg−1·day−1; Met), calorically restricted (70% of AL; CR), or calorically restricted and given metformin (CR+Met) for 12 weeks. Met lowered adiposity compared with AL but not to the same magnitude as CR or CR+Met (p < 0.05). Although only CR improved fasting insulin and glucose, the combination of CR+Met was needed to improve post-challenge glucose tolerance. All treatments lowered hepatic triglycerides, but further improvements were observed in the CR groups (p < 0.05, Met vs. CR or CR+Met) and a further reduction in serum alanine aminotransferases was observed in CR+Met rats. CR lowered markers of hepatic de novo lipogenesis (fatty acid synthase, acetyl-CoA carboxylase (ACC), and stearoyl-CoA desaturase-1 (SCD-1)) and increased hepatic mitochondrial activity (palmitate oxidation and β-hydroxyacyl CoA dehydrogenase (β-HAD) activity). Changes were enhanced in the CR+Met group for ACC, SCD-1, β-HAD, and the mitophagy marker BNIP3. Met decreased total hepatic mTOR content and inhibited mTOR complex 1, which may have contributed to Met-induced reductions in de novo lipogenesis. These findings in the OLETF rat suggest that the combination of caloric restriction and metformin may provide a more optimal approach than either treatment alone in the management of type 2 diabetes and NAFLD.

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A return to ad libitum feeding following caloric restriction promotes hepatic steatosis in hyperphagic OLETF rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00089.2016 ◽

2016 ◽

Vol 311 (3) ◽

pp. G387-G395 ◽

Cited By ~ 4

Author(s):

Melissa A. Linden ◽

Justin A. Fletcher ◽

Grace M. Meers ◽

John P. Thyfault ◽

M. Harold Laughlin ◽

...

Keyword(s):

Hepatic Steatosis ◽

Caloric Restriction ◽

Fatty Acid Synthase ◽

Cell Activation ◽

Citrate Synthase ◽

De Novo ◽

De Novo Lipogenesis ◽

Beneficial Effects ◽

Oletf Rats ◽

Ad Libitum

Hyperphagic Otsuka Long-Evans Tokushima fatty (OLETF) rats develop obesity, insulin resistance, and nonalcoholic fatty liver disease (NAFLD), but lifestyle modifications, such as caloric restriction (CR), can prevent these conditions. We sought to determine if prior CR had protective effects on metabolic health and NAFLD development following a 4-wk return to ad libitum (AL) feeding. Four-week-old male OLETF rats ( n = 8–10/group) were fed AL for 16 wk (O-AL), CR for 16 wk (O-CR; ∼70% kcal of O-AL), or CR for 12 wk followed by 4 wk of AL feeding (O-AL4wk). CR-induced benefit in prevention of NAFLD, including reduced hepatic steatosis, inflammation, and markers of Kupffer cell activation/number, was largely lost in AL4wk rats. These findings occurred in conjunction with a partial loss of CR-induced beneficial effects on obesity and serum triglycerides in O-AL4wk rats, but in the absence of changes in serum glucose or insulin. CR-induced increases in hepatic mitochondrial respiration remained significantly elevated ( P < 0.01) in O-AL4wk compared with O-AL rats, while mitochondrial [1-14C]palmitate oxidation, citrate synthase activity, and β-hydroxyacyl-CoA dehydrogenase activity did not differ among OLETF groups. NAFLD development in O-AL4wk rats was accompanied by increases in the protein content of the de novo lipogenesis markers fatty acid synthase and stearoyl-CoA desaturase-1 and decreases in phosphorylated acetyl-CoA carboxylase (pACC)/ACC compared with O-CR rats ( P < 0.05 for each). The beneficial effects of chronic CR on NAFLD development were largely lost with 4 wk of AL feeding in the hyperphagic OLETF rat, highlighting the importance of maintaining energy balance in the prevention of NAFLD.

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Short-term leptin infusion does not affect circulating levels of LH, testosterone or cortisol in food-restricted pubertal male rhesus macaques

Clinical Endocrinology ◽

10.1046/j.1365-2265.1999.00727.x ◽

1999 ◽

Vol 51 (1) ◽

pp. 41-51 ◽

Cited By ~ 21

Author(s):

Joaquin Lado-Abeal ◽

Yevgeniya O. Lukyanenko ◽

Sunita Swamy ◽

Ramon C. Hermida ◽

James C. Hutson ◽

...

Keyword(s):

Rhesus Macaques ◽

Short Term ◽

Circulating Levels ◽

Male Rhesus

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Allopurinol Prevents the Lipogenic Response Induced by an Acute Oral Fructose Challenge in Short-Term Fructose Fed Rats

Biomolecules ◽

10.3390/biom9100601 ◽

2019 ◽

Vol 9 (10) ◽

pp. 601 ◽

Cited By ~ 6

Author(s):

García-Arroyo ◽

Monroy-Sánchez ◽

Muñoz-Jiménez ◽

Gonzaga ◽

Andrés-Hernando ◽

...

Keyword(s):

Uric Acid ◽

Xanthine Oxidase ◽

Fatty Acid Synthase ◽

De Novo ◽

Tap Water ◽

De Novo Lipogenesis ◽

Sprague Dawley ◽

Short Term ◽

Alcoholic Fatty Liver ◽

High Fructose

We investigated whether short term high fructose intake may induce early hepatic dysfunction in rats and to test whether allopurinol treatment may have beneficial effects. Twenty male Sprague-Dawley rats received 20% fructose in drinking water (10 treated with allopurinol and 10 received vehicle) and 10 control rats received tap water. After 14 days, the hepatic response to an acute fructose load was evaluated, and in fasted animals, respirometry studies in freshly isolated mitochondria were performed. In fasting rats, we did not find differences in systemic or hepatic uric acid and triglyceride concentrations among the groups, but mitochondrial respiratory control rate was significantly decreased by high fructose feeding and correlated with a reduced expression of Complex I, as well as decreased aconitase-2 activity. On the other hand, in fructose fed rats, an acute fructose load increased systemic and hepatic uric acid, triglycerides and oxidative stress. Fructose feeding was also associated with fructokinase and xanthine oxidase overexpression and increased liver de novo lipogenesis program (fatty acid synthase (FAS) and cell death-inducing DFFA-like effector C (CIDEC) overexpression, ATP citrate lyase (ACL) and acetyl coA carboxylase (ACC) overactivity and decreased AMP-activated protein kinase (AMPk) and endothelial nitric oxide synthase (eNOS) activation). Allopurinol treatment prevented hepatic and systemic alterations. These data suggest that early treatment with xanthine oxidase inhibitors might provide a therapeutic advantage by delaying or even halting the progression of non-alcoholic fatty liver disease (NAFLD).

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Lipid Identification and Transcriptional Analysis of Controlling Enzymes in Bovine Ovarian Follicle

International Journal of Molecular Sciences ◽

10.3390/ijms19103261 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3261 ◽

Cited By ~ 12

Author(s):

Priscila Bertevello ◽

Ana-Paula Teixeira-Gomes ◽

Alexandre Seyer ◽

Anaïs Vitorino Carvalho ◽

Valérie Labas ◽

...

Keyword(s):

Lipid Metabolism ◽

Lipid Composition ◽

Molecular Mechanisms ◽

De Novo ◽

Ovarian Follicle ◽

Ovarian Follicles ◽

De Novo Lipogenesis ◽

Transcriptional Analysis ◽

Follicular Cells ◽

Metabolism Regulation

Ovarian follicle provides a favorable environment for enclosed oocytes, which acquire their competence in supporting embryo development in tight communications with somatic follicular cells and follicular fluid (FF). Although steroidogenesis in theca (TH) and granulosa cells (GC) is largely studied, and the molecular mechanisms of fatty acid (FA) metabolism in cumulus cells (CC) and oocytes are emerging, little data is available regarding lipid metabolism regulation within ovarian follicles. In this study, we investigated lipid composition and the transcriptional regulation of FA metabolism in 3–8 mm ovarian follicles in bovine. Using liquid chromatography and mass spectrometry (MS), 438 and 439 lipids were identified in FF and follicular cells, respectively. From the MALDI-TOF MS lipid fingerprints of FF, TH, GC, CC, and oocytes, and the MS imaging of ovarian sections, we identified 197 peaks and determined more abundant lipids in each compartment. Transcriptomics revealed lipid metabolism-related genes, which were expressed constitutively or more specifically in TH, GC, CC, or oocytes. Coupled with differential lipid composition, these data suggest that the ovarian follicle contains the metabolic machinery that is potentially capable of metabolizing FA from nutrient uptake, degrading and producing lipoproteins, performing de novo lipogenesis, and accumulating lipid reserves, thus assuring oocyte energy supply, membrane synthesis, and lipid-mediated signaling to maintain follicular homeostasis.

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