MicroRNA-29a in Osteoblasts Represses High-Fat Diet-Mediated Osteoporosis and Body Adiposis through Targeting Leptin

Skeletal tissue involves systemic adipose tissue metabolism and energy expenditure. MicroRNA signaling controls high-fat diet (HFD)-induced bone and fat homeostasis dysregulation remains uncertain. This study revealed that transgenic overexpression of miR-29a under control of osteocalcin promoter in osteoblasts (miR-29aTg) attenuated HFD-mediated body overweight, hyperglycemia, and hypercholesterolemia. HFD-fed miR-29aTg mice showed less bone mass loss, fatty marrow, and visceral fat mass together with increased subscapular brown fat mass than HFD-fed wild-type mice. HFD-induced O2 underconsumption, respiratory quotient repression, and heat underproduction were attenuated in miR-29aTg mice. In vitro, miR-29a overexpression repressed transcriptomic landscapes of the adipocytokine signaling pathway, fatty acid metabolism, and lipid transport, etc., of bone marrow mesenchymal progenitor cells. Forced miR-29a expression promoted osteogenic differentiation but inhibited adipocyte formation. miR-29a signaling promoted brown/beige adipocyte markers Ucp-1, Pgc-1α, P2rx5, and Pat2 expression and inhibited white adipocyte markers Tcf21 and Hoxc9 expression. The microRNA also reduced peroxisome formation and leptin expression during adipocyte formation and downregulated HFD-induced leptin expression in bone tissue. Taken together, miR-29a controlled leptin signaling and brown/beige adipocyte formation of osteogenic progenitor cells to preserve bone anabolism, which reversed HFD-induced energy underutilization and visceral fat overproduction. This study sheds light on a new molecular mechanism by which bone integrity counteracts HFD-induced whole-body fat overproduction.

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Antiobesity Effect of a Novel Herbal Formulation LI85008F in High-Fat Diet-Induced Obese Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6612996 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Hak Joo Choi ◽

Hwa Young Kim ◽

Kyoung Sik Park

Keyword(s):

Weight Gain ◽

Body Fat ◽

Fat Mass ◽

High Fat Diet ◽

Body Weight Gain ◽

Whole Body ◽

Body Fat Mass ◽

Obese Mice ◽

High Fat ◽

Herbal Formulation

A variety of natural products have been explored for their antiobesity potential and widely used to develop dietary supplements for the prevention of weight gain from excess body fat. In an attempt to find a natural antiobesity agent, this study was designed to evaluate the antiobesity activity of a novel herbal formulation LI85008F composed of extracts from three medicinal plants in high-fat diet- (HFD-) induced obese mice. After the thirteen-week oral administration of the test materials to mice, the body weight gain, whole-body fat mass, adipose tissue weight, and the expression levels of obesity-related proteins were measured. Our results indicated that LI85008F can suppress body weight gain and lower whole-body fat mass in HFD-induced obese mice. Significant decreases in epididymal and retroperitoneal fat mass were observed in LI85008F-treated groups compared with the HFD-fed control group ( p < 0.05 ). Furthermore, the oral administration of LI85008F caused significant decreases in the expression level of adipogenic (C/EBPα and PPARγ) and lipogenic (ACC) markers and notable increases in the production level of thermogenetic (AMPKα, PGC1α and UCP1) and lipolytic (HSL) proteins. These findings suggest that LI85008F holds great promise for a novel herbal formulation with antiobesity activities, preventing body fat accumulation and altering lipid metabolism.

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Dietary d-Psicose Reduced Visceral Fat Mass in High-Fat Diet-Induced Obese Rats

Journal of Food Science ◽

10.1111/j.1750-3841.2011.02571.x ◽

2012 ◽

Vol 77 (2) ◽

pp. H53-H58 ◽

Cited By ~ 33

Author(s):

Young-Mee Chung ◽

Joo Hyun Lee ◽

Deuk Youl Kim ◽

Se-Hee Hwang ◽

Young-Ho Hong ◽

...

Keyword(s):

Fat Mass ◽

Visceral Fat ◽

High Fat Diet ◽

High Fat ◽

Obese Rats

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The androgen receptor in bone marrow progenitor cells negatively regulates fat mass

Journal of Endocrinology ◽

10.1530/joe-17-0656 ◽

2018 ◽

Vol 237 (1) ◽

pp. 15-27 ◽

Cited By ~ 3

Author(s):

Patricia K Russell ◽

Salvatore Mangiafico ◽

Barbara C Fam ◽

Michele V Clarke ◽

Evelyn S Marin ◽

...

Keyword(s):

Bone Marrow ◽

Adipose Tissue ◽

Androgen Receptor ◽

Progenitor Cells ◽

Fat Mass ◽

Elevated Serum ◽

Gene Replacement ◽

Whole Body ◽

Clinical Aspects ◽

Mesenchymal Progenitor Cells

It is well established that testosterone negatively regulates fat mass in humans and mice; however, the mechanism by which testosterone exerts these effects is poorly understood. We and others have shown that deletion of the androgen receptor (AR) in male mice results in a phenotype that mimics the three key clinical aspects of hypogonadism in human males; increased fat mass and decreased bone and muscle mass. We now show that replacement of the Ar gene specifically in mesenchymal progenitor cells (PCs) residing in the bone marrow of Global-ARKO mice, in the absence of the AR in all other tissues (PC-AR Gene Replacements), completely attenuates their increased fat accumulation. Inguinal subcutaneous white adipose tissue and intra-abdominal retroperitoneal visceral adipose tissue depots in PC-AR Gene Replacement mice were 50–80% lower than wild-type (WT) and 75–90% lower than Global-ARKO controls at 12 weeks of age. The marked decrease in subcutaneous and visceral fat mass in PC-AR Gene Replacements was associated with an increase in the number of small adipocytes and a healthier metabolic profile compared to WT controls, characterised by normal serum leptin and elevated serum adiponectin levels. Euglycaemic/hyperinsulinaemic clamp studies reveal that the PC-AR Gene Replacement mice have improved whole-body insulin sensitivity with higher glucose infusion rates compared to WT mice and increased glucose uptake into subcutaneous and intra-abdominal fat. In conclusion, these data provide the first evidence for an action of androgens via the AR in mesenchymal bone marrow PCs to negatively regulate fat mass and improve metabolic function.

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DHEA protects against visceral obesity and muscle insulin resistance in rats fed a high-fat diet

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.273.5.r1704 ◽

1997 ◽

Vol 273 (5) ◽

pp. R1704-R1708 ◽

Cited By ~ 20

Author(s):

Polly A. Hansen ◽

Dong Ho Han ◽

Lorraine A. Nolte ◽

May Chen ◽

John O. Holloszy

Keyword(s):

Insulin Resistance ◽

Food Intake ◽

Protective Effect ◽

Fat Mass ◽

Visceral Fat ◽

High Fat Diet ◽

Visceral Obesity ◽

High Fat ◽

Muscle Insulin Resistance

Visceral obesity is frequently associated with muscle insulin resistance. Rats fed a high-fat diet rapidly develop obesity and insulin resistance. Dehydroepiandrosterone (DHEA) has been reported to protect against the development of obesity. This study tested the hypothesis that DHEA protects against the increase in visceral fat and the development of muscle insulin resistance induced by a high-fat diet in rats. Feeding rats a diet providing 50% of the energy as fat for 4 wk resulted in a twofold greater visceral fat mass and a 50% lower rate of maximally insulin-stimulated muscle 2-deoxyglucose (2-DG) uptake compared with controls. Rats fed the high-fat diet plus 0.3% DHEA were largely protected against the increase in visceral fat (+11.3 g in high fat vs. +2.9 g in high fat plus DHEA, compared with controls) and against the decrease in insulin-stimulated muscle 2-DG uptake (0.94 ± 0.15 μmol ⋅ ml−1 ⋅ 20 min−1, controls; 0.46 ± 0.06 μmol ⋅ ml−1 ⋅ 20 min−1, high-fat diet; 0.78 ± 0.07 μmol ⋅ ml−1 ⋅ 20 min−1, high fat + DHEA). DHEA did not affect food intake. These results show that DHEA has a protective effect against accumulation of visceral fat and development of muscle insulin resistance in rats fed a high-fat diet.

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High-fat diet-induced muscle insulin resistance: relationship to visceral fat mass

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2000.279.6.r2057 ◽

2000 ◽

Vol 279 (6) ◽

pp. R2057-R2065 ◽

Cited By ~ 89

Author(s):

Jong-Yeon Kim ◽

Lorraine A. Nolte ◽

Polly A. Hansen ◽

Dong-Ho Han ◽

Kevin Ferguson ◽

...

Keyword(s):

Insulin Resistance ◽

Fish Oil ◽

Fat Mass ◽

Visceral Fat ◽

High Fat Diet ◽

Corn Oil ◽

High Fat ◽

Muscle Insulin Resistance ◽

Visceral Fat Accumulation ◽

Fat Feeding

It has been variously hypothesized that the insulin resistance induced in rodents by a high-fat diet is due to increased visceral fat accumulation, to an increase in muscle triglyceride (TG) content, or to an effect of diet composition. In this study we used a number of interventions: fish oil, leptin, caloric restriction, and shorter duration of fat feeding, to try to disassociate an increase in visceral fat from muscle insulin resistance. Substituting fish oil (18% of calories) for corn oil in the high-fat diet partially protected against both the increase in visceral fat and muscle insulin resistance without affecting muscle TG content. Injections of leptin during the last 4 days of a 4-wk period on the high-fat diet partially reversed the increase in visceral fat and the muscle insulin resistance, while completely normalizing muscle TG. Restricting intake of the high-fat diet to 75% of ad libitum completely prevented the increase in visceral fat and muscle insulin resistance. Maximally insulin-stimulated glucose transport was negatively correlated with visceral fat mass ( P < 0.001) in both the soleus and epitrochlearis muscles and with muscle TG concentration in the soleus ( P < 0.05) but not in the epitrochlearis. Thus we were unable to dissociate the increase in visceral fat from muscle insulin resistance using a variety of approaches. These results support the hypothesis that an increase in visceral fat is associated with development of muscle insulin resistance.

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p53 Functions in Adipose Tissue Metabolism and Homeostasis

International Journal of Molecular Sciences ◽

10.3390/ijms19092622 ◽

2018 ◽

Vol 19 (9) ◽

pp. 2622 ◽

Cited By ~ 23

Author(s):

Jelena Krstic ◽

Isabel Reinisch ◽

Michael Schupp ◽

Tim Schulz ◽

Andreas Prokesch

Keyword(s):

Adipose Tissue ◽

Fat Mass ◽

High Fat Diet ◽

Nutrient Sensing ◽

Negative Regulator ◽

Model Systems ◽

Whole Body ◽

High Fat ◽

P53 Expression ◽

Brown Adipose

As a tumor suppressor and the most frequently mutated gene in cancer, p53 is among the best-described molecules in medical research. As cancer is in most cases an age-related disease, it seems paradoxical that p53 is so strongly conserved from early multicellular organisms to humans. A function not directly related to tumor suppression, such as the regulation of metabolism in nontransformed cells, could explain this selective pressure. While this role of p53 in cellular metabolism is gradually emerging, it is imperative to dissect the tissue- and cell-specific actions of p53 and its downstream signaling pathways. In this review, we focus on studies reporting p53’s impact on adipocyte development, function, and maintenance, as well as the causes and consequences of altered p53 levels in white and brown adipose tissue (AT) with respect to systemic energy homeostasis. While whole body p53 knockout mice gain less weight and fat mass under a high-fat diet owing to increased energy expenditure, modifying p53 expression specifically in adipocytes yields more refined insights: (1) p53 is a negative regulator of in vitro adipogenesis; (2) p53 levels in white AT are increased in diet-induced and genetic obesity mouse models and in obese humans; (3) functionally, elevated p53 in white AT increases senescence and chronic inflammation, aggravating systemic insulin resistance; (4) p53 is not required for normal development of brown AT; and (5) when p53 is activated in brown AT in mice fed a high-fat diet, it increases brown AT temperature and brown AT marker gene expression, thereby contributing to reduced fat mass accumulation. In addition, p53 is increasingly being recognized as crucial player in nutrient sensing pathways. Hence, despite existence of contradictory findings and a varying density of evidence, several functions of p53 in adipocytes and ATs have been emerging, positioning p53 as an essential regulatory hub in ATs. Future studies need to make use of more sophisticated in vivo model systems and should identify an AT-specific set of p53 target genes and downstream pathways upon different (nutrient) challenges to identify novel therapeutic targets to curb metabolic diseases.

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