Leptin: a pivotal regulator of human energy homeostasis

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.

Download Full-text

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

Download Full-text

Genetic and physiological analysis of the role of uncoupling proteins in human energy homeostasis

Journal of Molecular Medicine ◽

10.1007/s001090000150 ◽

2000 ◽

Vol 79 (1) ◽

pp. 48-56 ◽

Cited By ~ 63

Author(s):

Claire Pecqueur ◽

Elodie Couplan ◽

Frédéric Bouillaud ◽

Daniel Ricquier

Keyword(s):

Energy Homeostasis ◽

Uncoupling Proteins ◽

Human Energy ◽

Physiological Analysis

Download Full-text

Genetic and physiologic analysis of the role of uncoupling protein 3 in human energy homeostasis

Diabetes ◽

10.2337/diabetes.48.9.1890 ◽

1999 ◽

Vol 48 (9) ◽

pp. 1890-1895 ◽

Cited By ~ 38

Author(s):

W. K. Chung ◽

A. Luke ◽

R. S. Cooper ◽

C. Rotini ◽

A. Vidal-Puig ◽

...

Keyword(s):

Energy Homeostasis ◽

Uncoupling Protein ◽

Uncoupling Protein 3 ◽

Human Energy

Download Full-text

Sex-Specific Associations between Gut Prevotellaceae and Host Genetics on Adiposity

Microorganisms ◽

10.3390/microorganisms8060938 ◽

2020 ◽

Vol 8 (6) ◽

pp. 938

Author(s):

Amanda Cuevas-Sierra ◽

José Ignacio Riezu-Boj ◽

Elizabeth Guruceaga ◽

Fermín Ignacio Milagro ◽

José Alfredo Martínez

Keyword(s):

Genetic Background ◽

Energy Homeostasis ◽

Genetic Risk Score ◽

Normal Weight ◽

Dietary Advice ◽

Nucleotide Polymorphisms ◽

Linear Regression Models ◽

Metabolic Complications ◽

Human Energy ◽

Obese Subjects

The gut microbiome has been recognized as a tool for understanding adiposity accumulation and for providing personalized nutrition advice for the management of obesity and accompanying metabolic complications. The genetic background is also involved in human energy homeostasis. In order to increase the value of nutrigenetic dietary advice, the interplay between genetics and microbiota must be investigated. The purpose of the present study was to evaluate interactive associations between gut microbiota composition and 95 obesity-related single nucleotide polymorphisms (SNPs) searched in the literature. Oral mucosa and fecal samples from 360 normal weight, overweight and obese subjects were collected. Next generation genotyping of these 95 SNPs and fecal 16S rRNA sequencing were performed. A genetic risk score (GRS) was constructed with 10 SNPs statistically or marginally associated with body mass index (BMI). Several microbiome statistical analyses at family taxonomic level were applied (LEfSe, Canonical Correspondence Analysis, MetagenomeSeq and Random Forest), and Prevotellaceae family was found in all of them as one of the most important bacterial families associated with BMI and GRS. Thus, in this family it was further analyzed the interactive association between BMI and GRS with linear regression models. Interestingly, women with higher abundance of Prevotellaceae and higher GRS were more obese, compared to women with higher GRS and lower abundance of Prevotellaceae. These findings suggest relevant interrelationships between Prevotellaceae and the genetic background that may determine interindividual BMI differences in women, which opens the way to new precision nutrition-based treatments for obesity.

Download Full-text

The gut microbiota in human energy homeostasis and obesity

Trends in Endocrinology and Metabolism ◽

10.1016/j.tem.2015.07.002 ◽

2015 ◽

Vol 26 (9) ◽

pp. 493-501 ◽

Cited By ~ 188

Author(s):

Michael Rosenbaum ◽

Rob Knight ◽

Rudolph L. Leibel

Keyword(s):

Gut Microbiota ◽

Energy Homeostasis ◽

Human Energy

Download Full-text

The utility of animal models of human energy homeostasis

British Journal Of Nutrition ◽

10.1079/bjn20041141 ◽

2004 ◽

Vol 92 (S1) ◽

pp. S41-S45 ◽

Cited By ~ 15

Author(s):

Louise Thibault ◽

Stephen C. Woods ◽

Margriet S. Westerterp-Plantenga

Keyword(s):

Animal Models ◽

Energy Homeostasis ◽

Genetic Basis ◽

Genetic Factors ◽

Sedentary Lifestyle ◽

Human Energy ◽

Prevalence Of Obesity ◽

Adults And Children ◽

Environmental Causes

The prevalence of obesity among adults and children has increased steadily over the last few years worldwide, reaching epidemic proportions. Particularly alarming is the link between obesity and the development of chronic disorders such as heart disease, type 2 diabetes, hypertension and some cancers (Bjorntorp, 1997). Environmental causes of obesity are thought to include a sedentary lifestyle and an abundance of highly palatable energy-dense foods (Hill et al. 2003). Genetic factors also contribute to susceptibility to obesity, although the genetic basis of most human obesities is thought to be polygenic (Comuzzie & Allison, 1998; Barsh et al. 2000). The present paper considers some of the animal models used to infer aspects of human obesity, with an emphasis upon their usefulness.

Download Full-text

Fetal programming of human energy homeostasis brain networks: Issues and considerations

Obesity Reviews ◽

10.1111/obr.13392 ◽

2021 ◽

Author(s):

Jerod M. Rasmussen ◽

Paul M. Thompson ◽

Sonja Entringer ◽

Claudia Buss ◽

Pathik D. Wadhwa

Keyword(s):

Fetal Programming ◽

Energy Homeostasis ◽

Brain Networks ◽

Human Energy

Download Full-text

Proopiomelanocortin and Energy Balance: Insights from Human and Murine Genetics

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2004-0428 ◽

2004 ◽

Vol 89 (6) ◽

pp. 2557-2562 ◽

Cited By ~ 137

Author(s):

Anthony P. Coll ◽

I. Sadaf Farooqi ◽

Benjamin G. Challis ◽

Giles S. H. Yeo ◽

Stephen O’Rahilly

Keyword(s):

Energy Balance ◽

Energy Homeostasis ◽

Skin Pigmentation ◽

Biologically Active ◽

Melanocortin System ◽

Active Peptides ◽

Adrenal Steroidogenesis ◽

Human Energy ◽

Biologically Active Peptides ◽

Synthesis And Processing

Abstract Proopiomelanocortin (POMC) undergoes extensive and tissuespecific posttranslational processing to yield a range of biologically active peptides. Historically, the most clearly defined roles of these peptides are in the control of adrenal steroidogenesis by corticotroph-derived ACTH and skin pigmentation by αMSH. However, a rapidly expanding body of work has established that POMC-derived peptides synthesized in neurons of the hypothalamus play a central role in the control of energy homeostasis. We review how inherited abnormalities in POMC synthesis and processing and defects in the action of POMC-derived peptides in both humans and mice have helped shape our current understanding of the importance of the melanocortin system in human energy balance.

Download Full-text