scholarly journals Role of Medium- and Short-Chain L-3-Hydroxyacyl-CoA Dehydrogenase in the Regulation of Body Weight and Thermogenesis

Endocrinology ◽  
2011 ◽  
Vol 152 (12) ◽  
pp. 4641-4651 ◽  
Author(s):  
Nadja Schulz ◽  
Heinz Himmelbauer ◽  
Michaela Rath ◽  
Michel van Weeghel ◽  
Sander Houten ◽  
...  
Keyword(s):  
Body Weight ◽  
Insulin Secretion ◽  
Body Temperature ◽  
Knockout Mice ◽  
Fuel Efficiency ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Obese Mouse ◽  
Acid Oxidation ◽  
Trait Locus

Dysregulation of fatty acid oxidation plays a pivotal role in the pathophysiology of obesity and insulin resistance. Medium- and short-chain-3-hydroxyacyl-coenzyme A (CoA) dehydrogenase (SCHAD) (gene name, hadh) catalyze the third reaction of the mitochondrial β-oxidation cascade, the oxidation of 3-hydroxyacyl-CoA to 3-ketoacyl-CoA, for medium- and short-chain fatty acids. We identified hadh as a putative obesity gene by comparison of two genome-wide scans, a quantitative trait locus analysis previously performed in the polygenic obese New Zealand obese mouse and an earlier described small interfering RNA-mediated mutagenesis in Caenorhabditis elegans. In the present study, we show that mice lacking SCHAD (hadh−/−) displayed a lower body weight and a reduced fat mass in comparison with hadh+/+ mice under high-fat diet conditions, presumably due to an impaired fuel efficiency, the loss of acylcarnitines via the urine, and increased body temperature. Food intake, total energy expenditure, and locomotor activity were not altered in knockout mice. Hadh−/− mice exhibited normal fat tolerance at 20 C. However, during cold exposure, knockout mice were unable to clear triglycerides from the plasma and to maintain their normal body temperature, indicating that SCHAD plays an important role in adaptive thermogenesis. Blood glucose concentrations in the fasted and postprandial state were significantly lower in hadh−/− mice, whereas insulin levels were elevated. Accordingly, insulin secretion in response to glucose and glucose plus palmitate was elevated in isolated islets of knockout mice. Therefore, our data indicate that SCHAD is involved in thermogenesis, in the maintenance of body weight, and in the regulation of nutrient-stimulated insulin secretion.

scholarly journals Effect of milk replacer allowance on calf faecal bacterial community profiles and fermentation

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Sandeep Kumar ◽  
M. Ajmal Khan ◽  
Emma Beijer ◽  
Jinxin Liu ◽  
Katherine K. Lowe ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Body Weight ◽  
Bacterial Community ◽  
Bacterial Diversity ◽  
Serum Protein ◽  
Bacterial Communities ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Milk Replacer ◽  
Protein Levels

Abstract Background The nutrition of calves from birth until weaning is predominantly from liquid (milk or milk-based) feeds. Liquid feed allowances are often restricted during artificial rearing to accelerate the development of the rumen by promoting solid feed intake. Liquid feeds bypass the rumen and are digested in the lower digestive tract, however, the influence of different types of milk feeds, and their allowances, on the calf hindgut microbiota is not well understood. In this study, faecal samples from 199 calves raised on three different allowances of milk replacer: 10% of initial bodyweight (LA), 20% of initial bodyweight (HA), and ad libitum (ADLIB), were collected just prior to weaning. Bacterial community structures and fermentation products were analysed, and their relationships with calf growth and health parameters were examined to identify potential interactions between diet, gut microbiota and calf performance. Results Differences in the total concentrations of short-chain fatty acids were not observed, but higher milk replacer allowances increased the concentrations of branched short-chain fatty acids and decreased acetate to propionate ratios. The bacterial communities were dominated by Ruminococcaceae, Lachnospiraceae and Bacteroides, and the bacterial diversity of the ADLIB diet group was greater than that of the other diet groups. Faecalibacterium was over three times more abundant in the ADLIB compared to the LA group, and its abundance correlated strongly with girth and body weight gains. Milk replacer intake correlated strongly with Peptococcus and Blautia, which also correlated with body weight gain. Bifidobacterium averaged less than 1% abundance, however its levels, and those of Clostridium sensu stricto 1, correlated strongly with initial serum protein levels, which are an indicator of colostrum intake and passive transfer of immunoglobulins in early life. Conclusions Higher milk replacer intakes in calves increased hindgut bacterial diversity and resulted in bacterial communities and short chain fatty acid profiles associated with greater protein fermentation. Increased abundances of beneficial bacteria such as Faecalibacterium, were also observed, which may contribute to development and growth. Moreover, correlations between microbial taxa and initial serum protein levels suggest that colostrum intake in the first days of life may influence microbiota composition at pre-weaning.

scholarly journals Regulation of energy expenditure and substrate oxidation by short-chain fatty acids

2019 ◽  
Vol 242 (2) ◽  
pp. R1-R8 ◽  
Author(s):  
Alia H Sukkar ◽  
Aaron M Lett ◽  
Gary Frost ◽  
Edward S Chambers
Keyword(s):  
Fatty Acids ◽  
Body Weight ◽  
Weight Gain ◽  
Energy Expenditure ◽  
Lipid Oxidation ◽  
Dietary Fibre ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Present Review

Short-chain fatty acids (SCFAs) are metabolites produced from the fermentation of dietary fibre by the gut microbiota. High-fibre diets have been associated with lower weight gain and a number of reports have therefore investigated if these positive effects of a dietary fibre on body weight can be replicated through the direct administration of SCFAs. Many of these studies have reported that SCFAs can prevent or attenuate long-term body weight gain by increasing energy expenditure through increased lipid oxidation. The aim of the present review is to therefore evaluate the current evidence for an effect of SCFAs on whole-body energy expenditure and to assess the potential underlying mechanisms. The available data highlights that SCFAs can exert multiple effects at various organ and tissue sites that would cumulatively raise energy expenditure via a promotion of lipid oxidation. In conclusion, the present review proposes that dietary interventions and other therapies that augment gut-derived SCFAs and systemic availability may present an effective strategy to improve long-term energy balance and body weight management.

Expression of carnitine palmitoyl-CoA transferase-1B is influenced by a cis-acting eQTL in two chicken lines selected for high and low body weight

2013 ◽  
Vol 45 (9) ◽  
pp. 367-376 ◽  
Author(s):  
Sojeong Ka ◽  
Ellen Markljung ◽  
Henrik Ring ◽  
Frank W. Albert ◽  
Mohammad Harun-Or-Rashid ◽  
...  
Keyword(s):  
Body Weight ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Differentially Expressed ◽  
Acid Oxidation ◽  
Altered Expression ◽  
Cis Acting ◽  
Chromosome 1P ◽  
Coa Transferase ◽  
Trait Locus

Carnitine palmitoyl-CoA transferase-1B is a mitochondrial enzyme in the fatty acid oxidation pathway. In a previous study, CPT1B was identified as differentially expressed in the hypothalamus of two lines of chickens established by long-term selection for high (HWS) or low (LWS) body weight. Mammals have three paralogs ( CPT1a, b and c) while nonmammalian vertebrates only have two ( CPT1A, B). CPT1A is expressed in liver and CPT1B in muscle. CPT1c is expressed in hypothalamus, where it regulates feeding and energy expenditure. We identified an intronic length polymorphism, fixed for different alleles in the two populations, and mapped the hitherto missing CPT1B locus in the chicken genome assembly, to the distal tip of chromosome 1p. Based on molecular phylogeny and gene synteny we suggest that chicken CPT1B is pro-orthologous of the mammalian CPT1c. Chicken CPT1B was differentially expressed in both muscle and hypothalamus but in opposite directions: higher levels in hypothalamus but lower levels in muscle in the HWS than in the LWS line. Using an advanced intercross population of the lines, we found CPT1B expression to be influenced by a cis-acting expression quantitative trait locus in muscle. The increased expression in hypothalamus and reduced expression in muscle is consistent with an increased food intake in the HWS line and at the same time reduced fatty acid oxidation in muscle yielding a net accumulation of energy intake and storage. The altered expression of CPT1B in hypothalamus and peripheral tissue is likely to be a mechanism contributing to the remarkable difference between lines.

scholarly journals Elaiophylin reduces body weight and lowers glucose levels in obese mice by activating AMPK

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Ruoxuan Bao ◽  
Yongmei Meng ◽  
Haibo Zhang ◽  
Chen Yang ◽  
Wei Li ◽  
...  
Keyword(s):  
Body Weight ◽  
Chronic Diseases ◽  
Therapeutic Potential ◽  
In Vivo Studies ◽  
Pharmacological Intervention ◽  
Obese Mouse ◽  
Acid Oxidation ◽  
Dependent Manner ◽  
Glucose Levels ◽  
Treatment Of Obesity

AbstractObesity is an epidemic affecting 13% of the global population and increasing the risk of many chronic diseases. However, only several drugs are licensed for pharmacological intervention for the treatment of obesity. As a master regulator of metabolism, the therapeutic potential of AMPK is widely recognized and aggressively pursued for the treatment of metabolic diseases. We found that elaiophylin (Ela) rapidly activates AMPK in a panel of cancer-cell lines, as well as primary hepatocytes and adipocytes. Meanwhile, Ela inhibits the mTORC1 complex, turning on catabolism and turning off anabolism together with AMPK. In vitro and in vivo studies showed that Ela does not activate AMPK directly, instead, it increases cellular AMP/ATP and ADP/ATP ratios, leading to AMPK phosphorylation in a LKB1-dependent manner. AMPK activation induced by Ela caused changes in diverse metabolic genes, thereby promoting glucose consumption and fatty acid oxidation. Importantly, Ela activates AMPK in mouse liver and adipose tissue. As a consequence, it reduces body weight and blood glucose levels and improves glucose and insulin tolerance in both ob/ob and high-fat diet-induced obese mouse models. Our study has identified a novel AMPK activator as a candidate drug for the treatment of obesity and its associated chronic diseases.

Regulation of Insulin Secretion by Short Chain Fatty Acids

Nature ◽  
1968 ◽  
Vol 217 (5131) ◽  
pp. 853-853 ◽  
Author(s):  
W. MONTAGUE ◽  
K. W. TAYLOR
Keyword(s):  
Fatty Acids ◽  
Insulin Secretion ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Chain Fatty Acids

scholarly journals Effects of Prebiotics, Probiotics, and Synbiotics on the Bodyweight, Blood Glucose, Triglyceride and TNF-α of Diet-induced Obesity Rats

2020 ◽  
Vol 4 (2) ◽  
pp. 247
Author(s):  
Lenny Octavia ◽  
Soebagijo Adi Soelistijo ◽  
Agung Dwi Wahyu Widodo
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
High Fat Diet ◽  
Short Chain Fatty Acids ◽  
The Body ◽  
Male Rats ◽  
Acid Oxidation ◽  
Low Grade ◽  
High Fat ◽  
Tnf Α

Abstract  High-fat diet leads to obesity-associated chronic low-grade inflammation. Prebiotics, probiotics, and synbiotics produced short-chain fatty acids (SCFA), bonded to G protein-coupled receptors (GPR)-41 and GPR-43 decreased triglyceride deposits in adipocytes and liver, decreased fatty acid oxidation, increased glucose regulation and insulin sensitivity thus reduced the risk of obesity and metabolic syndrome. This study conducted in order to evaluate the effects of prebiotics, probiotics, and synbiotics on the body weight, blood glucose, triglyceride, and TNF-α used rats model, which were fed by a high-fat diet. Thirty-eight 6-8 weeks old male rats were fed by high-fat diet for three weeks, then rats were randomly divided into four groups, high-fat diet (HFD), a high fat diet with prebiotics supplementation (HFD+ PRE), a high fat diet with probiotics supplementation (HFD+PRO), and high-fat diet with synbiotics supplementation (HFD+SYN) for three weeks. Blood samples and body weight were measured at the third and sixth week. There was no effect of prebiotics, probiotics, and synbiotics on body weight, triglyceride levels, blood glucose, and TNF-α in rats fed a high-fat diet compared to control. These results suggested that supplementations gave inconsistent results with other studies and needed further researches.Keywords             : high fat diet, prebiotics, probiotics, synbiotics, meta-inflammationCorrespondence   : [email protected]

scholarly journals Controversial Roles of Gut Microbiota-Derived Short-Chain Fatty Acids (SCFAs) on Pancreatic β-Cell Growth and Insulin Secretion

2020 ◽  
Vol 21 (3) ◽  
pp. 910 ◽  
Author(s):  
Jun-Li Liu ◽  
Irina Segovia ◽  
Xiao-Lin Yuan ◽  
Zu-hua Gao
Keyword(s):  
Fatty Acids ◽  
Insulin Secretion ◽  
Gut Microbiota ◽  
Metabolic Regulation ◽  
Glucose Production ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Β Cell ◽  
Disease Associations ◽  
Chain Fatty Acids

In the past 15 years, gut microbiota emerged as a crucial player in health and disease. Enormous progress was made in the analysis of its composition, even in the discovery of novel species. It is time to go beyond mere microbiota-disease associations and, instead, provide more causal analyses. A key mechanism of metabolic regulation by the gut microbiota is through the production of short-chain fatty acids (SCFAs). Acting as supplemental nutrients and specific ligands of two G-protein-coupled receptors (GPCRs), they target the intestines, brain, liver, and adipose tissue, and they regulate appetite, energy expenditure, adiposity, and glucose production. With accumulating but sometimes conflicting research results, key questions emerged. Do SCFAs regulate pancreatic islets directly? What is the effect of β-cell-specific receptor deletions? What are the mechanisms used by SCFAs to regulate β-cell proliferation, survival, and secretion? The receptors FFA2/3 are normally expressed on pancreatic β-cells. Deficiency in FFA2 may have caused glucose intolerance and β-cell deficiency in mice. However, this was contrasted by a double-receptor knockout. Even more controversial are the effects of SCFAs on insulin secretion; there might be no direct effect at all. Unable to draw clear conclusions, this review reveals some of the recent controversies.

Short-chain fatty acids in control of body weight and insulin sensitivity

2015 ◽  
Vol 11 (10) ◽  
pp. 577-591 ◽  
Author(s):  
Emanuel E. Canfora ◽  
Johan W. Jocken ◽  
Ellen E. Blaak
Keyword(s):  
Fatty Acids ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Chain Fatty Acids

Short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with hyperinsulinism: a novel glucose–fatty acid cycle?

2003 ◽  
Vol 31 (6) ◽  
pp. 1137-1139 ◽  
Author(s):  
S. Eaton ◽  
I. Chatziandreou ◽  
S. Krywawych ◽  
S. Pen ◽  
P.T. Clayton ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Dehydrogenase Deficiency ◽  
Short Chain ◽  
Acid Oxidation ◽  
Β Cells ◽  
Molecular Defects ◽  
Glucose Fatty Acid Cycle ◽  
Hydroxyacyl Coa Dehydrogenase

Hyperinsulinism of infancy is caused by inappropriate insulin secretion in pancreatic β-cells, even when blood glucose is low. Several molecular defects are known to cause hyperinsulinism of infancy, such as KATP channelopathies and regulatory defects of glucokinase and glutamate dehydrogenase. Although defects of fatty acid oxidation have not previously been known to cause hyperinsulinism, patients with deficiency in SCHAD (short-chain 3-hydroxyacyl-CoA dehydrogenase; an enzyme of mitochondrial β-oxidation) have hyperinsulinism. A novel link between fatty acid oxidation and insulin secretion may explain hyperinsulinism in these patients.

scholarly journals Fiber Diet-Mediated Increases in Short Chain Fatty Acids Alleviate Western Diet Induced Metabolic Dysfunction

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1175-1175
Author(s):  
Medha Priyadarshini ◽  
Md Wasim Khan ◽  
Kai Xu ◽  
Jade Yeh ◽  
Barton Wicksteed ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Body Weight ◽  
Phase I ◽  
Phase Ii ◽  
Time Course ◽  
Control Diet ◽  
Short Chain Fatty Acids ◽  
Western Diet ◽  
Short Chain ◽  
Chain Fatty Acids

Abstract Objectives Short chain fatty acids (SCFAs), which are gut microbial fermentation byproducts with suggested positive health effects, have emerged as a therapeutic modality against metabolic diseases like obesity and type 2 diabetes. Alluringly, in vivo SCFA levels are easily modifiable by consumption of fermentable fibers (FF). Most rodent studies on dietary FF supplementation report terminal increased cecal/fecal SCFA levels but the time course of this increase remains elusive. Also, there is limited information on the effect of this sustained SCFA increase on physiology. Thus, we investigated dietary FF-dependent temporal increases in plasma SCFA levels and its metabolic effects on a western diet (WD) mouse model. Methods C57BL/6J male mice (age 10 weeks) were fed test diets for 8 weeks. In Phase I, to establish time-course of plasma SCFA increase, mice were fed the following isocaloric diets: control (low fat + 0% FF); WD; control + 20% FF, where FF was fructooligosaccharides (FOS), inulin (In), guar gum (GG) or pectin (Pec). In Phase II mice were fed a control diet, or a WD with or without 20% FOS, Pec or GG. End points were weekly plasma SCFAs (by MS/MS), body weight, random glucose and insulin, and at the end of experimental period body fat composition and metabolic tests. Results Phase I. Compared to control, WD lowered while FF induced significant increases in total plasma SCFAs (FOS, Pec, GG > In) in a time dependent manner that plateaued beyond 2 weeks. All FF increased propionate and acetate but not butyrate. Phase II. WD caused metabolic dysfunctions (increased body weight and fat mass; glucose intolerance; insulin resistance; P < 0.0001 by two-way ANOVA) that were alleviated in mice fed FF enriched WD (Pec = GG > FOS). Compared to WD, food intake was similar except high in the WD-Pec group, while WD-Pec and GG showed higher energy expenditure. All 3 plasma SCFAs were significantly higher in all WD-FF groups. FF supplementation of the control diet showed no significant difference compared to control. Conclusions We conclude that: 1) FF feeding induced SCFA production reaches saturation within 2 weeks, suggesting selection of specific gut bacterial features; and 2) all FFs were protective from weight gain and its metabolic consequences. Funding Sources 2R01 DK104927 (NIH/NIDDK) Layden.

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