The gut microbiota in human energy homeostasis and obesity

A decrease in ovarian estrogens in postmenopausal women increases the risk of weight gain, cardiovascular disease, type 2 diabetes, and chronic inflammation. While it is known that gut microbiota regulates energy homeostasis, it is unclear if gut microbiota is associated with estradiol regulation of metabolism. In this study, we tested if estradiol-mediated protection from high-fat diet (HFD)-induced obesity and metabolic changes are associated with longitudinal alterations in gut microbiota in female mice. Ovariectomized adult mice with vehicle or estradiol (E2) implants were fed chow for two weeks and HFD for four weeks. As reported previously, E2 increased energy expenditure, physical activity, insulin sensitivity, and whole-body glucose turnover. Interestingly, E2 decreased the tight junction protein occludin, suggesting E2 affects gut epithelial integrity. Moreover, E2 increased Akkermansia and decreased Erysipleotrichaceae and Streptococcaceae. Furthermore, Coprobacillus and Lactococcus were positively correlated, while Akkermansia was negatively correlated, with body weight and fat mass. These results suggest that changes in gut epithelial barrier and specific gut microbiota contribute to E2-mediated protection against diet-induced obesity and metabolic dysregulation. These findings provide support for the gut microbiota as a therapeutic target for treating estrogen-dependent metabolic disorders in women.

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Abstract P247: Gut Microbiota From A Rat Model Of Metabolic Syndrome Lowers Fitness Of High Exercise Capacity Rats (HCR/ Tol ) By Impairing Energy Homeostasis And Increasing Blood Pressure

Hypertension ◽

10.1161/hyp.76.suppl_1.p247 ◽

2020 ◽

Vol 76 (Suppl_1) ◽

Author(s):

Guannan Zhou ◽

Tao Yang ◽

Sivarajan Kumarasamy ◽

Bina Joe ◽

Lauren G Koch

Keyword(s):

Blood Pressure ◽

Metabolic Syndrome ◽

Energy Metabolism ◽

Gut Microbiota ◽

Exercise Capacity ◽

Energy Homeostasis ◽

Current Knowledge ◽

Strong Predictor ◽

Whole Body ◽

Acid Oxidation

Introduction: Low exercise capacity is a strong predictor of cardiovascular disease and overall mortality. Previously we have shown that rats artificially selected for low intrinsic exercise capacity (LCR) have reduced longevity and develop features consistent with metabolic syndrome (MetS) compared to high intrinsic exercise capacity rats (HCR). Current knowledge suggests that gut microbiota is an important contributor for host fitness. Thus, we hypothesized that transferring gut microbiota from LCR rats into inbred high capacity runner (HCR /Tol ) rats would increase risk factors for MetS, including high blood pressure (BP), gain in body weight (BW), and altered resting energy metabolism. Methods: Gut microbiota was depleted in male HCR/ Tol rats (4 mo.) by an antibiotic cocktail given orally (50mg/kg of BW/day) for 5 days, followed by weekly fecal microbiota transfer (FMT) from male LCR or HCR rats (13 mo.) to generate HCR/ Tol -LCR FMT (n = 5) or HCR/ Tol -HCR FMT (n = 6) groups. BW was measured every 4 weeks. At week 11, whole body metabolism was measured by indirect calorimetry (Oxymax, Columbus Instruments). Respiratory Exchange Ratio (RER), Energy Expenditure (EE), glucose and fat oxidation were calculated from oxygen consumption and carbon dioxide release (VO 2 and VCO 2 ). At week 12, BP was measured by tail-cuff method (Kent Scientific) and treadmill exercise test was done at week 13. Results: Compared to HCR/ Tol -HCR FMT , HCR/ Tol -LCR FMT showed a significant gain in BW (7.2% vs 1.9%, P<0.05), elevated systolic BP (147 vs 120 mmHg, P<0.0001), diastolic BP (112 vs 91 mmHg, P<0.01), and mean BP (123 vs 100 mmHg, P<0.001). BP changes in HCR/ Tol -LCR FMT associated with 1) increased VO 2 (355 vs 320 ml/hr, P<0.05), 2) elevated VCO 2 (350 vs 298 ml/hr, P<0.01), 3) increased EE (1.8 vs 1.6 kcal/hr, P<0.01), 4) higher RER (0.96 vs 0.91, P<0.001), 5) higher glucose oxidation (1.36 vs 1.12 g/kg/hr, P<0.001) and 6) reduced fatty acid oxidation (0.09 vs 0.15 g/kg/hr, P<0.01) and a 23% lower exercise capacity. Conclusions: Gut microbiota from LCR rats strongly associated with poor health outcomes, notably elevated BP and impaired energy metabolism. These findings suggest that altered energy homeostasis by microbiota is mechanistically linked to host BP regulation within MetS.

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Leptin: a pivotal regulator of human energy homeostasis

American Journal of Clinical Nutrition ◽

10.3945/ajcn.2008.26788c ◽

2009 ◽

Vol 89 (3) ◽

pp. 980S-984S ◽

Cited By ~ 197

Author(s):

I Sadaf Farooqi ◽

Stephen O’Rahilly

Keyword(s):

Energy Homeostasis ◽

Human Energy

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Effect ofLactobacillus acidophilusNCDC 13 supplementation on the progression of obesity in diet-induced obese mice

British Journal Of Nutrition ◽

10.1017/s0007114511006957 ◽

2012 ◽

Vol 108 (8) ◽

pp. 1382-1389 ◽

Cited By ~ 58

Author(s):

Tulika Arora ◽

Jelena Anastasovska ◽

Glen Gibson ◽

Kieran Tuohy ◽

Raj Kumar Sharma ◽

...

Keyword(s):

Gut Microbiota ◽

Body Fat ◽

Energy Homeostasis ◽

Dietary Intervention ◽

Body Weight Gain ◽

Starter Cultures ◽

Whole Body ◽

Fat Composition ◽

Muscle Adiposity ◽

Mri Changes

There is an increased interest in investigating the relationship between the gut microbiota and energy homeostasis. Probiotics are health beneficial microbes mainly categorised under the genusLactobacillusandBifidobacterium, which when administered in adequate amounts confer health benefits to the host, and have been implicated in various physiological functions. The potential role of probiotics in energy homeostasis is a current and an emerging area of research. In the present study,Lactobacillus acidophilusNCDC 13 was used to evaluate its anti-obesity potential in diet-induced obese (C57BL/6) mice. The probiotic bacterial culture was administered in Indian yogurt preparation called ‘dahi’, prepared using native starter cultures, and compared with control dahi containing only dahi starter cultures. The dietary intervention was followed for 8 weeks, and whole-body fat composition, and liver and muscle adiposity were measured using MRI. Changes in gut microbiota were assessed by fluorescentin situhybridisation in faeces and caecal contents. The feeding of the probiotic brought no changes in body-weight gain, food and dahi intake when compared with the control dahi-fed animals. No significant changes in body fat composition, liver and muscle adiposity were also observed. At the end of the dietary intervention, a significant increase (P < 0·05) in the number of totalBifidobacteriumwas observed in both faeces and caecal contents of mice as a result of probiotic dahi administration. Thus,L. acidophilusNCDC 13 supplementation could be beneficial in shifting the gut microbiota balance positively. However, its anti-obesity potential could not be established in the present study and warrants further exploration.

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The long isoform uncoupling protein-3 (UCP3L) in human energy homeostasis

International Journal of Obesity ◽

10.1038/sj.ijo.0800945 ◽

1999 ◽

Vol 23 (S6) ◽

pp. S49-S50 ◽

Cited By ~ 4

Author(s):

WK Chung ◽

A Luke ◽

RS Cooper ◽

C Rotini ◽

A Vidal-Puig ◽

...

Keyword(s):

Energy Homeostasis ◽

Uncoupling Protein ◽

Uncoupling Protein 3 ◽

Human Energy

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The regulation of body weight: lessons from the seasonal animal

Proceedings of The Nutrition Society ◽

10.1079/pns200060 ◽

2001 ◽

Vol 60 (1) ◽

pp. 127-134 ◽

Cited By ~ 32

Author(s):

Peter J. Morgan ◽

Julian G. Mercer

Keyword(s):

Body Weight ◽

Energy Balance ◽

Energy Homeostasis ◽

Mutant Mouse ◽

Neural Pathways ◽

Control Mechanisms ◽

Gene Deletions ◽

Regulate Body Weight ◽

Human Energy ◽

Ingestive Behaviour

The hypothalamus is a major regulatory centre involved in the control of many important physiological axes. One of these axes is the regulation of ingestive behaviour. Recent work using a combination of genetic-mutant mouse models together with targeted gene deletions has contributed much to our understanding of how neural pathways of the hypothalamus are involved in the regulation of energy balance in animals. These pathways are also relevant to human energy homeostasis, as mutations in key genes are correlated with obesity. Many of the genes identified mediate the effects of leptin, and are therefore primarily involved in sensing and responding to peripheral signals. In seasonal animals, such as the Siberian hamster (Phodopus sungorus), there is evidence for a higher level of regulation. The systems involved regulate body weight around an apparent 'set-point' through the action of photoperiod via the neurohormone, melatonin. The ability to manipulate energy balance through photoperiod (and melatonin) in the seasonal-animal model offers novel opportunities to identify further fundamental aspects of the control mechanisms involved in the central control of energy homeostasis and body weight.

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Multi-Pharmacology of Berberine in Atherosclerosis and Metabolic Diseases: Potential Contribution of Gut Microbiota

Frontiers in Pharmacology ◽

10.3389/fphar.2021.709629 ◽

2021 ◽

Vol 12 ◽

Author(s):

Shengjie Yang ◽

Dan Li ◽

Zongliang Yu ◽

Yujuan Li ◽

Min Wu

Keyword(s):

Gut Microbiota ◽

Energy Homeostasis ◽

Metabolic Diseases ◽

Biological Effects ◽

Intestinal Barrier ◽

Isoquinoline Alkaloid ◽

Research Progress ◽

Intestinal Barrier Function ◽

Potential Contribution ◽

Nonalcoholic Fatty Liver

Atherosclerosis (AS), especially atherosclerotic cardiovascular diseases (ASCVDs), and metabolic diseases (such as diabetes, obesity, dyslipidemia, and nonalcoholic fatty liver disease) are major public health issues worldwide that seriously threaten human health. Exploring effective natural product-based drugs is a promising strategy for the treatment of AS and metabolic diseases. Berberine (BBR), an important isoquinoline alkaloid found in various medicinal plants, has been shown to have multiple pharmacological effects and therapeutic applications. In view of its low bioavailability, increasing evidence indicates that the gut microbiota may serve as a target for the multifunctional effects of BBR. Under the pathological conditions of AS and metabolic diseases, BBR improves intestinal barrier function and reduces inflammation induced by gut microbiota-derived lipopolysaccharide (LPS). Moreover, BBR reverses or induces structural and compositional alterations in the gut microbiota and regulates gut microbe-dependent metabolites as well as related downstream pathways; this improves glucose and lipid metabolism and energy homeostasis. These findings at least partly explain the effect of BBR on AS and metabolic diseases. In this review, we elaborate on the research progress of BBR and its mechanisms of action in the treatment of AS and metabolic diseases from the perspective of gut microbiota, to reveal the potential contribution of gut microbiota to the multifunctional biological effects of BBR.

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Gestational Diabetes, Colorectal Cancer, Bariatric Surgery, and Weight Loss among Diabetes Mellitus Patients: A Mini Review of the Interplay of Multispecies Probiotics

Nutrients ◽

10.3390/nu14010192 ◽

2021 ◽

Vol 14 (1) ◽

pp. 192

Author(s):

Emmanouil Benioudakis ◽

Eleni Karlafti ◽

Alexandra Bekiaridou ◽

Triantafyllos Didangelos ◽

Theodossis S. Papavramidis

Keyword(s):

Diabetes Mellitus ◽

Gut Microbiota ◽

Energy Homeostasis ◽

Healing Process ◽

Wound Healing Process ◽

Global Public Health ◽

Inflammatory Cytokine Production ◽

Increased Risk ◽

Central Food

Diabetes mellitus has been steadily increasing over the past decades and is one of the most significant global public health concerns. Diabetes mellitus patients have an increased risk of both surgical and post-surgical complications. The post-surgical risks are associated with the primary condition that led to surgery and the hyperglycaemia per se. Gut microbiota seems to contribute to glucose homeostasis and insulin resistance. It affects the metabolism through body weight and energy homeostasis, integrating the peripheral and central food intake regulatory signals. Homeostasis of gut microbiota seems to be enhanced by probiotics pre and postoperatively. The term probiotics is used to describe some species of live microorganisms that, when administered in adequate amounts, confer health benefits on the host. The role of probiotics in intestinal or microbial skin balance after abdominal or soft tissue elective surgeries on DM patients seems beneficial, as it promotes anti-inflammatory cytokine production while increasing the wound-healing process. This review article aims to present the interrelation of probiotic supplements with DM patients undergoing elective surgeries.

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The role of the molecular circadian clock in human energy homeostasis

Current Opinion in Lipidology ◽

10.1097/mol.0000000000000722 ◽

2020 ◽

Vol 32 (1) ◽

pp. 16-23

Author(s):

Lucile Dollet ◽

Logan A. Pendergrast ◽

Juleen R. Zierath

Keyword(s):

Circadian Clock ◽

Energy Homeostasis ◽

Human Energy

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Biological underpinnings from psychosocial stress towards appetite and obesity during youth: research implications towards metagenomics, epigenomics and metabolomics

Nutrition Research Reviews ◽

10.1017/s0954422419000143 ◽

2019 ◽

Vol 32 (2) ◽

pp. 282-293 ◽

Cited By ~ 6

Author(s):

Nathalie Michels

Keyword(s):

Gut Microbiota ◽

Psychosocial Stress ◽

Emotional Eating ◽

Energy Homeostasis ◽

Stress Reactivity ◽

Gastrointestinal Hormones ◽

Biological Factor ◽

Oral Microbiota ◽

Central Adiposity ◽

Reward Pathways

AbstractPsychosocial stress, uncontrolled eating and obesity are three interrelated epidemiological phenomena already present during youth. This broad narrative conceptual review summarises main biological underpinnings of the stress–diet–obesity pathway and how new techniques can further knowledge. Cortisol seems the main biological factor from stress towards central adiposity; and diet, physical activity and sleep are the main behavioural pathways. Within stress–diet, the concepts of comfort food and emotional eating are highlighted, as cortisol affects reward pathways and appetite brain centres with a role for insulin, leptin, neuropeptide Y (NPY), endocannabinoids, orexin and gastrointestinal hormones. More recently researched biological underpinnings are microbiota, epigenetic modifications and metabolites. First, the gut microbiota reaches the stress-regulating and appetite-regulating brain centres via the gut–brain axis. Second, epigenetic analyses are recommended as diet, obesity, stress and gut microbiota can change gene expression which then affects appetite, energy homeostasis and stress reactivity. Finally, metabolomics would be a good technique to disentangle stress–diet–obesity interactions as multiple biological pathways are involved. Saliva might be an ideal biological matrix as it allows metagenomic (oral microbiota), epigenomic and metabolomic analyses. In conclusion, stress and diet/obesity research should be combined in interdisciplinary collaborations with implementation of several -omics analyses.

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