Specific skeletal muscle sphingolipid compounds in energy expenditure regulation and weight gain in Native Americans of Southwestern heritage

Obesity is a major health problem worldwide, given its growing incidence and its association with a variety of comorbidities. Weight gain results from an increase in energy intake without a concomitant increase in energy expenditure. To combat the obesity epidemic, many studies have focused on the pathways underlying satiety and hunger signaling, while other studies have concentrated on the mechanisms involved in energy expenditure, most notably adaptive thermogenesis. Hypothyroidism in humans is typically associated with a decreased basal metabolic rate, lower energy expenditure, and weight gain. However, hypothyroid mouse models have been reported to have a leaner phenotype than euthyroid controls. To elucidate the mechanism underlying this phenomenon, we used a drug-free mouse model of hypothyroidism: mice lacking the sodium/iodide symporter (NIS), the plasma membrane protein that mediates active iodide uptake in the thyroid. In addition to being leaner than euthyroid mice, owing in part to reduced food intake, these hypothyroid mice show signs of compensatory up-regulation of the skeletal-muscle adaptive thermogenic marker sarcolipin, with an associated increase in fatty acid oxidation (FAO). Neither catecholamines nor thyroid-stimulating hormone (TSH) are responsible for sarcolipin expression or FAO stimulation; rather, thyroid hormones are likely to negatively regulate both processes in skeletal muscle. Our findings indicate that hypothyroidism in mice results in a variety of metabolic changes, which collectively lead to a leaner phenotype. A deeper understanding of these changes may make it possible to develop new strategies against obesity.

Download Full-text

A combination of exercise and capsinoid supplementation additively suppresses diet-induced obesity by increasing energy expenditure in mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00354.2014 ◽

2015 ◽

Vol 308 (4) ◽

pp. E315-E323 ◽

Cited By ~ 37

Author(s):

Kana Ohyama ◽

Yoshihito Nogusa ◽

Katsuya Suzuki ◽

Kosaku Shinoda ◽

Shingo Kajimura ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Energy Expenditure ◽

Body Weight Gain ◽

Whole Body ◽

Voluntary Running ◽

Running Wheel Exercise ◽

Body Energy

Exercise effectively prevents the development of obesity and obesity-related diseases such as type 2 diabetes. Capsinoids (CSNs) are capsaicin analogs found in a nonpungent pepper that increase whole body energy expenditure. Although both exercise and CSNs have antiobesity functions, the effectiveness of exercise with CSN supplementation has not yet been investigated. Here, we examined whether the beneficial effects of exercise could be further enhanced by CSN supplementation in mice. Mice were randomly assigned to four groups: 1) high-fat diet (HFD, Control), 2) HFD containing 0.3% CSNs, 3) HFD with voluntary running wheel exercise (Exercise), and 4) HFD containing 0.3% CSNs with voluntary running wheel exercise (Exercise + CSN). After 8 wk of ingestion, blood and tissues were collected and analyzed. Although CSNs significantly suppressed body weight gain under the HFD, CSN supplementation with exercise additively decreased body weight gain and fat accumulation and increased whole body energy expenditure compared with exercise alone. Exercise together with CSN supplementation robustly improved metabolic profiles, including the plasma cholesterol level. Furthermore, this combination significantly prevented diet-induced liver steatosis and decreased the size of adipocyte cells in white adipose tissue. Exercise and CSNs significantly increased cAMP levels and PKA activity in brown adipose tissue (BAT), indicating an increase of lipolysis. Moreover, they significantly activated both the oxidative phosphorylation gene program and fatty acid oxidation in skeletal muscle. These results indicate that CSNs efficiently promote the antiobesity effect of exercise, in part by increasing energy expenditure via the activation of fat oxidation in skeletal muscle and lipolysis in BAT.

Download Full-text

Combination of Canagliflozin and Exercise Training Leads to Lipid-Dependent Energy Expenditure in Skeletal Muscle in Obese Diabetic Mice

Diabetes ◽

10.2337/db18-742-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 742-P

Author(s):

KENICHI TANAKA ◽

HIROKAZU TAKAHASHI ◽

KAZUYO SASAKI ◽

KANAKO INOUE ◽

YAYOI MATSUDA ◽

...

Keyword(s):

Skeletal Muscle ◽

Energy Expenditure ◽

Exercise Training ◽

Diabetic Mice

Download Full-text

Low Resting Energy Expenditure Is Associated with High Gestational Weight Gain Only When Resting Energy Expenditure Fluctuates

Reproductive Sciences ◽

10.1007/s43032-021-00544-z ◽

2021 ◽

Author(s):

Krista S. Leonard ◽

Zita Oravecz ◽

Danielle Symons Downs

Keyword(s):

Weight Gain ◽

Energy Expenditure ◽

Gestational Weight Gain ◽

Resting Energy Expenditure ◽

Gestational Weight ◽

Resting Energy

Download Full-text

Front Cover: Nicotinamide Protects Against Diet‐Induced Body Weight Gain, Increases Energy Expenditure, and Induces White Adipose Tissue Beiging

Molecular Nutrition & Food Research ◽

10.1002/mnfr.202170027 ◽

2021 ◽

Vol 65 (11) ◽

pp. 2170027

Author(s):

Karen Alejandra Méndez‐Lara ◽

Elisabeth Rodríguez‐Millán ◽

David Sebastián ◽

Rosi Blanco‐Soto ◽

Mercedes Camacho ◽

...

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Energy Expenditure ◽

White Adipose Tissue ◽

Body Weight Gain ◽

Front Cover

Download Full-text

β-Adrenergically Stimulated Fat Oxidation Is Diminished in Middle-Aged Compared to Young Subjects*

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.84.10.6043 ◽

1999 ◽

Vol 84 (10) ◽

pp. 3764-3769

Author(s):

E. E. Blaak ◽

M. A. van Baak ◽

W. H. M. Saris

Keyword(s):

Skeletal Muscle ◽

Energy Expenditure ◽

Total Energy ◽

Fat Oxidation ◽

Substrate Utilization ◽

Total Energy Expenditure ◽

Adrenergic Stimulation ◽

Middle Aged ◽

Older Subjects ◽

Young Subjects

Abstract The effect of aging on β-adrenergically mediated substrate utilization was investigated in nine young (25.2 ± 1.7 yr old) and eight older males (52.9 ± 2.1 yr old), matched for body weight and body composition. In a first experiment, the nonselectiveβ -agonist isoprenaline (ISO) was infused in increasing standardized doses, and during each infusion period energy expenditure and substrate utilization were determined by indirect calorimetry. In a second experiment, forearm skeletal muscle metabolism was studied during a standardized infusion dose of ISO (19 ng/kg fat-free mass·min). During β-adrenergic stimulation there was an increased carbohydrate oxidation (at an ISO infusion dose of 24 ng/kg fat-free mass·min, 31% vs. 21% of total energy expenditure; P < 0.05) and a decreased fat oxidation (51 vs. 62 of total energy expenditure; P < 0.05) in older compared to young subjects. Skeletal muscle lactate release significantly increased in the older subjects (from −175 ± 32 to −366 ± 66 nmol/100 mL forearm tissue·min), whereas there was no change in young subjects (from− 32 ± 21 to 23 ± 57 nmol/100 mL forearm tissue·min; interaction group × ISO, P < 0.01). Additionally, there was a tendency toward a blunted ISO-induced increase in nonesterified fatty acid uptake in the older subjects (interaction group × ISO, P = 0.062). Thus, middle-aged subjects have a blunted ability to oxidize fat during β-adrenergic stimulation compared to young subjects. This diminished fat oxidation may be an important etiological factor in the age-related increase in body fatness and obesity by favoring fat storage above oxidation.

Download Full-text

Female rats selectively bred for high intrinsic aerobic fitness are protected from ovariectomy-associated metabolic dysfunction

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00401.2014 ◽

2015 ◽

Vol 308 (6) ◽

pp. R530-R542 ◽

Cited By ~ 34

Author(s):

Victoria J. Vieira-Potter ◽

Jaume Padilla ◽

Young-Min Park ◽

Rebecca J. Welly ◽

Rebecca J. Scroggins ◽

...

Keyword(s):

Physical Activity ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Energy Expenditure ◽

Aerobic Fitness ◽

Resting Energy Expenditure ◽

Female Rats ◽

Metabolic Dysfunction ◽

Spontaneous Physical Activity ◽

Resting Energy

Ovariectomized rodents model human menopause in that they rapidly gain weight, reduce spontaneous physical activity (SPA), and develop metabolic dysfunction, including insulin resistance. How contrasting aerobic fitness levels impacts ovariectomy (OVX)-associated metabolic dysfunction is not known. Female rats selectively bred for high and low intrinsic aerobic fitness [high-capacity runners (HCR) and low-capacity runners (LCR), respectively] were maintained under sedentary conditions for 39 wk. Midway through the observation period, OVX or sham (SHM) operations were performed providing HCR-SHM, HCR-OVX, LCR-SHM, and LCR-OVX groups. Glucose tolerance, energy expenditure, and SPA were measured before and 4 wk after surgery, while body composition via dual-energy X-ray absorptiometry and adipose tissue distribution, brown adipose tissue (BAT), and skeletal muscle phenotype, hepatic lipid content, insulin resistance via homeostatic assessment model of insulin resistance and AdipoIR, and blood lipids were assessed at death. Remarkably, HCR were protected from OVX-associated increases in adiposity and insulin resistance, observed only in LCR. HCR rats were ∼30% smaller, had ∼70% greater spontaneous physical activity (SPA), consumed ∼10% more relative energy, had greater skeletal muscle proliferator-activated receptor coactivator 1-alpha, and ∼40% more BAT. OVX did not increase energy intake and reduced SPA to the same extent in both HCR and LCR. LCR were particularly affected by an OVX-associated reduction in resting energy expenditure and experienced a reduction in relative BAT; resting energy expenditure correlated positively with BAT across all animals ( r = 0.6; P < 0.001). In conclusion, despite reduced SPA following OVX, high intrinsic aerobic fitness protects against OVX-associated increases in adiposity and insulin resistance. The mechanism may involve preservation of resting energy expenditure.

Download Full-text

Minimal impact of age and housing temperature on the metabolic phenotype of Acc2−/− mice

Journal of Endocrinology ◽

10.1530/joe-15-0444 ◽

2015 ◽

Vol 228 (3) ◽

pp. 127-134 ◽

Cited By ~ 6

Author(s):

Amanda E Brandon ◽

Ella Stuart ◽

Simon J Leslie ◽

Kyle L Hoehn ◽

David E James ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Composition ◽

Energy Expenditure ◽

Glucose Tolerance ◽

Fat Mass ◽

Knockout Mice ◽

Muscle Glycogen ◽

Insulin Action ◽

Metabolic Phenotype ◽

Whole Body

An important regulator of fatty acid oxidation (FAO) is the allosteric inhibition of CPT-1 by malonyl-CoA produced by the enzyme acetyl-CoA carboxylase 2 (ACC2). Initial studies suggested that deletion of Acc2 (Acacb) increased fat oxidation and reduced adipose tissue mass but in an independently generated strain of Acc2 knockout mice we observed increased whole-body and skeletal muscle FAO and a compensatory increase in muscle glycogen stores without changes in glucose tolerance, energy expenditure or fat mass in young mice (12–16 weeks). The aim of the present study was to determine whether there was any effect of age or housing at thermoneutrality (29 °C; which reduces total energy expenditure) on the phenotype of Acc2 knockout mice. At 42–54 weeks of age, male WT and Acc2−/− mice had similar body weight, fat mass, muscle triglyceride content and glucose tolerance. Consistent with younger Acc2−/− mice, aged Acc2−/− mice showed increased whole-body FAO (24 h average respiratory exchange ratio=0.95±0.02 and 0.92±0.02 for WT and Acc2−/− mice respectively, P<0.05) and skeletal muscle glycogen content (+60%, P<0.05) without any detectable change in whole-body energy expenditure. Hyperinsulinaemic–euglycaemic clamp studies revealed no difference in insulin action between groups with similar glucose infusion rates and tissue glucose uptake. Housing Acc2−/− mice at 29 °C did not alter body composition, glucose tolerance or the effects of fat feeding compared with WT mice. These results confirm that manipulation of Acc2 may alter FAO in mice, but this has little impact on body composition or insulin action.

Download Full-text