scholarly journals The sedentary (r)evolution: Have we lost our metabolic flexibility?

F1000Research ◽  
2018 ◽  
Vol 6 ◽  
pp. 1787 ◽  
Author(s):  
Jens Freese ◽  
Rainer Johannes Klement ◽  
Begoña Ruiz-Núñez ◽  
Sebastian Schwarz ◽  
Helmut Lötzerich
Keyword(s):  
Metabolic Diseases ◽  
Sedentary Lifestyle ◽  
Metabolic Flexibility ◽  
Alcoholic Fatty Liver ◽  
Modern Times ◽  
The Metabolic Syndrome ◽  
Agricultural Revolution ◽  
Energy Needs ◽  
Lack Of Exercise

During the course of evolution, up until the agricultural revolution, environmental fluctuations forced the human species to develop a flexible metabolism in order to adapt its energy needs to various climate, seasonal and vegetation conditions. Metabolic flexibility safeguarded human survival independent of food availability. In modern times, humans switched their primal lifestyle towards a constant availability of energy-dense, yet often nutrient-deficient, foods, persistent psycho-emotional stressors and a lack of exercise. As a result, humans progressively gain metabolic disorders, such as the metabolic syndrome, type 2 diabetes, non-alcoholic fatty liver disease, certain types of cancer, cardiovascular disease and Alzheimer´s disease, wherever the sedentary lifestyle spreads in the world. For more than 2.5 million years, our capability to store fat for times of food shortage was an outstanding survival advantage. Nowadays, the same survival strategy in a completely altered surrounding is responsible for a constant accumulation of body fat. In this article, we argue that the metabolic disease epidemic is largely based on a deficit in metabolic flexibility. We hypothesize that the modern energetic inflexibility, typically displayed by symptoms of neuroglycopenia, can be reversed by re-cultivating suppressed metabolic programs, which became obsolete in an affluent environment, particularly the ability to easily switch to ketone body and fat oxidation. In a simplified model, the basic metabolic programs of humans’ primal hunter-gatherer lifestyle are opposed to the current sedentary lifestyle. Those metabolic programs, which are chronically neglected in modern surroundings, are identified and conclusions for the prevention of chronic metabolic diseases are drawn.

scholarly journals The sedentary (r)evolution: Have we lost our metabolic flexibility?

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1787 ◽  
Author(s):  
Jens Freese ◽  
Rainer Johannes Klement ◽  
Begoña Ruiz-Núñez ◽  
Sebastian Schwarz ◽  
Helmut Lötzerich
Keyword(s):  
Metabolic Diseases ◽  
Sedentary Lifestyle ◽  
Metabolic Flexibility ◽  
Alcoholic Fatty Liver ◽  
Modern Times ◽  
The Metabolic Syndrome ◽  
Agricultural Revolution ◽  
Energy Needs ◽  
Lack Of Exercise

During the course of evolution, up until the agricultural revolution, environmental fluctuations forced the human species to develop a flexible metabolism in order to adapt its energy needs to various climate, seasonal and vegetation conditions. Metabolic flexibility safeguarded human survival independent of food availability. In modern times, humans switched their primal lifestyle towards a constant availability of energy-dense, yet often nutrient-deficient, foods, persistent psycho-emotional stressors and a lack of exercise. As a result, humans progressively gain metabolic disorders, such as the metabolic syndrome, type 2 diabetes, non-alcoholic fatty liver disease, certain types of cancer, cardiovascular disease and Alzheimer´s disease, wherever the sedentary lifestyle spreads in the world. For more than 2.5 million years, our capability to store fat for times of food shortage was an outstanding survival advantage. Nowadays, the same survival strategy in a completely altered surrounding is responsible for a constant accumulation of body fat. In this article, we argue that the metabolic epidemic is largely based on a deficit in metabolic flexibility. We hypothesize that the modern energetic inflexibility, typically displayed by symptoms of neuroglycopenia, can be reversed by re-cultivating suppressed metabolic programs, which became obsolete in an affluent environment, particularly the ability to easily switch to ketone body and fat oxidation. In a simplified model, the basic metabolic programs of humans’ primal hunter-gatherer lifestyle are opposed to the current sedentary lifestyle. Those metabolic programs, which are chronically neglected in modern surroundings, are identified and conclusions for the prevention of chronic metabolic diseases are drawn.

Bile acids and the metabolic syndrome

2019 ◽  
Vol 56 (3) ◽  
pp. 326-337 ◽  
Author(s):  
Emma Rose McGlone ◽  
Stephen R Bloom
Keyword(s):  
Diabetes Mellitus ◽  
Bile Acid ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Metabolic Effects ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Alcoholic Fatty Liver Disease

Bile acids have important roles in the regulation of lipid, glucose and energy metabolism. Metabolic diseases linked to obesity, including type 2 diabetes mellitus and non-alcoholic fatty liver disease, are associated with dysregulation of bile acid homeostasis. Here, the basic chemistry and regulation of bile acids as well as their metabolic effects will be reviewed. Changes in circulating bile acids associated with obesity and related diseases will be reviewed. Finally, pharmaceutical manipulation of bile acid homeostasis as therapy for metabolic diseases will be outlined.

scholarly journals Non-Alcoholic Fatty Liver in Patients with Chylomicronemia

2021 ◽  
Vol 10 (4) ◽  
pp. 669
Author(s):  
Mélanie Maltais ◽  
Diane Brisson ◽  
Daniel Gaudet
Keyword(s):  
Acute Pancreatitis ◽  
Fatty Liver ◽  
Transient Elastography ◽  
Very Low Density Lipoproteins ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Main Driver ◽  
Liver Ultrasonography

Non-alcoholic fatty liver disease (NAFLD) is frequent in patients with features of the metabolic syndrome (MetS), obesity, or type 2 diabetes. Lipoprotein lipase (LPL) is the main driver of triglyceride (TG) hydrolysis in chylomicrons and very-low density lipoproteins (VLDL). In some patients with MetS, dysfunction of this pathway can lead to plasma TG values > 10 mmol/L (multifactorial chylomicronemia or MCS). Chylomicronemia also characterizes LPL deficiency (LPLD), a rare autosomal recessive disease called familial chylomicronemia syndrome (FCS), which is associated with an increased risk of recurrent pancreatitis. This study aims to investigate the expression of NAFLD, as assessed by transient elastography, in MCS and FCS subjects. Data were obtained from 38 subjects with chylomicronemia; 19 genetically confirmed FCS and 19 sex- and age-matched MCS. All participants underwent liver ultrasonography and stiffness measurement after a 4-h fast using transient elastography (FibroScan®, Echosens, Waltham, MA, USA). NAFLD (controlled attenuation parameter (CAP) > 280 dB/m) was observed in 42.1% of FCS and 73.7% of MCS subjects (p = 0.05). FCS subjects had lower body mass index (BMI) than MCS. Only 25% of FCS subjects with NAFLD had a BMI ≥ 30 compared to 64.3% in MCS (p = 0.004). In FCS, NAFLD occurred even in the presence of very low (≤18 kg/m2) BMI. In both FCS and MCS, CAP was negatively associated with acute pancreatitis risk. In this study, NAFLD was commonly observed in both FCS and MCS subjects and occurred independently of the BMI and fasting glucose values in FCS; NAFLD was associated with a lower occurrence of acute pancreatitis episodes.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: FXR signalling: a novel target in metabolic diseases

2021 ◽  
Vol 184 (5) ◽  
pp. R193-R205
Author(s):  
David P Sonne
Keyword(s):  
Type 2 Diabetes ◽  
Bile Acid ◽  
Gastrointestinal Tract ◽  
Glucose Metabolism ◽  
Metabolic Diseases ◽  
Farnesoid X Receptor ◽  
Optimal Size ◽  
Lipid Digestion ◽  
Alcoholic Fatty Liver

During the last decades, it has become clear that the gastrointestinal tract plays a pivotal role in the regulation of glucose homeostasis. More than 40 hormones originate from the gastrointestinal tract and several of these impact glucose metabolism and appetite regulation. An astonishing example of the gut’s integrative role in glucose metabolism originates from investigations into bile acid biology. From primary animal studies, it has become clear that bile acids should no longer be labelled as simple detergents necessary for lipid digestion and absorption but should also be recognised as metabolic regulators implicated in lipid, glucose and energy metabolism. The nuclear farnesoid X receptor (FXR) is a part of an exquisite bile acid-sensing system that among other things ensures the optimal size of the bile acid pool. In addition, intestinal and hepatic FXR also impact the regulation of several metabolic processes such as glucose and lipid metabolism. Accordingly, natural and synthetic FXR agonists and certain FXR-regulated factors (i.e. fibroblast growth factor 19 (FGF19)) are increasingly being evaluated as treatments for metabolic diseases such as type 2 diabetes and non-alcoholic fatty liver disease (and its inflammatory version, non-alcoholic steatohepatitis). Interestingly, decreased FXR activation also benefits glucose metabolism. This can be obtained by reducing bile acid absorption using bile acid sequestering agents (approved for the treatment of type 2 diabetes) or inhibitors of intestinal bile acid transporters,that is the apical sodium-dependent bile acid transporter (ASBT). This article discusses recent clinical trials that provide insights about the role of FXR-FGF19-targetted therapy for the treatment of metabolic diseases.

Endoscopic Duodenal Mucosal Resurfacing for the Treatment of Type 2 Diabetes

2018 ◽  
Vol 36 (4) ◽  
pp. 322-324 ◽  
Author(s):  
Alia Hadefi ◽  
Vincent Huberty ◽  
Arnaud Lemmers ◽  
Marianna Arvanitakis ◽  
David Maggs ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bypass Surgery ◽  
Metabolic Diseases ◽  
Invasive Procedure ◽  
Diabetic Patients ◽  
Intestinal Bypass ◽  
Alcoholic Fatty Liver ◽  
Glucose Homoeostasis ◽  
Alcoholic Fatty Liver Disease

Type 2 diabetes is a pandemic disease with an incidence that has risen steadily over recent decades. Experimental evidence in animals has demonstrated that intestinal bypass surgery of the upper small intestine, particularly the duodenum, has an important role in glucose homoeostasis. Furthermore, Roux-en-Y bypass performed as bariatric surgery has shown to correct hyperglycaemia from the first postoperative days in obese diabetic patients. Therefore, on the basis of these considerations, duodenal mucosal resurfacing was studied in type 2 diabetes patients as a minimally invasive procedure that could offer an alternative treatment for these patients. Further studies, and particularly large controlled trials, are needed to determine the place of this procedure in the treatment of type 2 diabetes as well as other metabolic diseases such as non-alcoholic fatty liver disease/non-alcoholic steatohepatitis.

Blood triacylglycerols: a lipidomic window on diet and disease

2016 ◽  
Vol 44 (2) ◽  
pp. 638-644 ◽  
Author(s):  
Francis Sanders ◽  
Ben McNally ◽  
Julian L. Griffin
Keyword(s):  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Clinical Chemistry ◽  
Total Concentration ◽  
Direct Infusion ◽  
Alcoholic Fatty Liver ◽  
Tissue Extracts ◽  
The Individual ◽  
Alcoholic Fatty Liver Disease

Although the measurement of triacylglycerols (TAGs) by clinical chemistry has been used in the diagnosis of a range of metabolic diseases, such approaches ignore the different species of TAGs that contribute to the total concentration. With the advent of LC and direct infusion forms of MS it is now possible to profile the individual TAGs in blood plasma or tissue extracts. This mini review surveys the information that is obtainable from the lipidomic profiling of TAGs in following metabolic diseases such as type 2 diabetes (T2DM), cardiovascular disease (CVD) and non-alcoholic fatty liver disease, as well as the development of insulin resistance and obesity.

scholarly journals Association between Lysosomal Dysfunction and Obesity-Related Pathology: A Key Knowledge to Prevent Metabolic Syndrome

2019 ◽  
Vol 20 (15) ◽  
pp. 3688 ◽  
Author(s):  
Yuhei Mizunoe ◽  
Masaki Kobayashi ◽  
Ryoma Tagawa ◽  
Yoshimi Nakagawa ◽  
Hitoshi Shimano ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Cerebrovascular Diseases ◽  
Alcoholic Fatty Liver ◽  
Glucose And Lipid Metabolism ◽  
Lysosome Biogenesis ◽  
The Metabolic Syndrome ◽  
Lysosomal Dysfunction ◽  
Lysosomal Proteases ◽  
The Relationship

Obesity causes various health problems, such as type 2 diabetes, non-alcoholic fatty liver disease, and cardio- and cerebrovascular diseases. Metabolic organs, particularly white adipose tissue (WAT) and liver, are deeply involved in obesity. WAT contains many adipocytes with energy storage capacity and secretes adipokines depending on the obesity state, while liver plays pivotal roles in glucose and lipid metabolism. This review outlines and underscores the relationship between obesity and lysosomal functions, including lysosome biogenesis, maturation and activity of lysosomal proteases in WAT and liver. It has been revealed that obesity-induced abnormalities of lysosomal proteases contribute to inflammation and cellular senescence in adipocytes. Previous reports have demonstrated obesity-induced ectopic lipid accumulation in liver is associated with abnormality of lysosomal proteases as well as other lysosomal enzymes. These studies demonstrate that lysosomal dysfunction in WAT and liver underlies part of the obesity-related pathology, raising the possibility that strategies to modulate lysosomal function may be effective in preventing or treating the metabolic syndrome.

Modulation of energy balance by fibroblast growth factor 21

2016 ◽  
Vol 30 (1) ◽  
Author(s):  
Daniel Cuevas-Ramos ◽  
Carlos A. Aguilar-Salinas
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Energy Balance ◽  
Energy Expenditure ◽  
Metabolic Diseases ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
The Metabolic Syndrome ◽  
Brown Adipose

AbstractFibroblast growth factors (FGFs) are a superfamily of 22 proteins related to cell proliferation and tissue repair after injury. A subgroup of three proteins, FGF19, FGF21, and FGF23, are major endocrine mediators. These three FGFs have low affinity to heparin sulfate during receptor binding; in contrast they have a strong interaction with the cofactor Klotho/β-Klotho. FGF21 has received particular attention because of its key role in carbohydrate, lipids, and energy balance regulation. FGF21 improves glucose and lipids metabolism as well as increasing energy expenditure in animal models and humans. Conditions that induce human physical stress such as exercise, lactation, obesity, insulin resistance, and type 2 diabetes influence FGF21 circulating levels. FGF21 also has an anti-oxidant function in human metabolic diseases which contribute to understanding the FGF21 compensatory increment in obesity, the metabolic syndrome, and type 2 diabetes. Interestingly, energy expenditure and weight loss is induced by FGF21. The mechanism involved is through “browning” of white adipose tissue, increasing brown adipose tissue activity and heat production. Therefore, clinical evaluation of therapeutic action of exogenous FGF21 administration is warranted, particularly to treat diabetes and obesity.

scholarly journals Anti-diabetic effects of palm fruit juice in the Nile rat (Arvicanthis niloticus)

2014 ◽  
Vol 3 ◽  
Author(s):  
Julia Bolsinger ◽  
Andrzej Pronczuk ◽  
Ravigadevi Sambanthamurthi ◽  
K. C. Hayes
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Fruit Juice ◽  
Metabolic Diseases ◽  
Fasting Blood Glucose ◽  
Diabetes Type 2 ◽  
Palm Fruit ◽  
The Metabolic Syndrome ◽  
Arvicanthis Niloticus

AbstractWith the increasing incidence of metabolic diseases, numerous bioactive phytochemicals have been proffered in the dietary prevention of these conditions. Palm fruit juice (PFJ) possesses bioactive phenolic compounds (referred to as oil palm phenolics; OPP) that may deter diabetes. The objective of the present experiments was to document the degree to which PFJ reduces diabetes symptoms in a variety of circumstances in the Nile rat (Arvicanthis niloticus), a novel model for carbohydrate-induced type 2 diabetes (type 2 diabetes mellitus; T2DM) and the metabolic syndrome. Wild-type male Nile rats (n 100) were fed laboratory chow or semi-purified diabetogenic diets in five experiments lasting 4–36 weeks. PFJ was provided as a drink or mixed into the diet to provide OPP intakes from 170 to 720 mg gallic acid equivalents/kg body weight per d. Body weight and random and fasting blood glucose were assessed at different time points, and were analysed along with terminal fasting organ weights, insulin, plasma and liver lipids as measures of diabetes progression. PFJ proved to be anti-hyperglycaemic and anti-lipaemic in all experiments relative to untreated controls, delaying T2DM onset and even reversing advancing diabetes. Protection by PFJ was directly related to its OPP content, and no negative effects on energy intake or growth were observed. PFJ was effective both as a drink and mixed into the diet. Results suggest that PFJ may slow the rate of glucose absorption, reduce insulin resistance and/or enhance insulin secretion.

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