Brain-derived neurotrophic factor modulates mitochondrial dynamics and thermogenic phenotype on 3T3-L1 adipocytes.

Obesity is a growing threat. In recent years, the finding of functional brown adipose tissue (BAT) in adult humans implemented the studies of anti-obesity therapies based on triggering energy expenditure. The activation of BAT thermogenesis and the recruitment of brite (brown-in-white) adipocytes are under noradrenergic control. Brain-derived neurotrophic factor (BDNF), if centrally administered, enhances thermogenesis through sympathetic activation, but its direct effect on adipocytes is still unclear. The phenotypic change from fat storing to thermogenic adipocytes is recognized by the presence of multilocular lipid droplets (LDs) and fissed mitochondria that tend to surround LDs, maximizing the efficiency of fatty acid release for thermogenesis. BDNF treatment on differentiated 3T3-L1 adipocytes was compared to negative (CTRL) and positive (norepinephrine, NE) controls. BDNF significantly increased small globular mitochondria percentage (>150% CTRL), while the area surface and elongation index of branched tubules were respectively 55% and 10% lower than NE. Canonical discriminant analysis of mitochondria morphological data clearly separated differentially treated cells with 85% of the total variance. The expression of brown markers and mitochondrial dynamic genes was significantly affected by BDNF. Investigating the pathways involved in adipocyte BDNF stimulation could clarify its role in thermogenesis and its possible local regulation.

Simpson-Golabi-Behmel syndrome human adipocytes reveal a changing phenotype throughout differentiation.

The Simpson-Golabi-Behmel syndrome (SGBS) cell strain is widely considered to be a representative in vitro model of human subcutaneous white pre-adipocytes. These cells achieve a transient expression of classical brown markers, such as uncoupling protein 1, peaking at day 14 of differentiation and decreasing thereafter. Adipocyte browning process involves dynamic changes in lipid droplet (LD) dimension, in mitochondria morphology, and in the expression of brown-specific marker genes. This study analyzes SGBS transient phenotypic transformation by quantifying the heterogeneity of LDs, mitochondrial dynamics, and a panel of genes involved in adipocyte differentiation and browning. LDs at 21 days of differentiation were larger than in the previous stages, without any change in the number per cell. The expression of genes such as peroxisome peroxisome proliferator-activated receptor γ, leptin, and lipase E significantly raised from 0 to 21 days. Adiponectin was significantly upregulated at 14 days of differentiation. Brown-specific marker PR domain containing 16 was highly expressed at D0. The variability of mitochondrial shape and interconnectivity reflects differences in the relative rates of fusion and fission, resulting in a significant shift from a networked shape at D7 to a fragmented and swollen one at D14 and D21. The transient phenotype experienced by this cellular model should be considered whether used in studies involving the stimulation of adipocyte browning and could be an interesting human model to further elucidate the browning process in the absence of any stimulation.

Factors involved in white-to-brown adipose tissue conversion and in thermogenesis: a review.

Obesity is the result of energy intake chronically exceeding energy expenditure. Classical treatments against obesity do not provide a satisfactory long-term outcome for the majority of patients. After the demonstration of functional brown adipose tissue in human adults, great effort is being devoted to develop therapies based on the adipose tissue itself, through the conversion of fat-accumulating white adipose tissue into energy-dissipating brown adipose tissue. Anti-obesity treatments that exploit endogenous, pharmacological and nutritional factors to drive such conversion are especially in demand. In the present review, we summarize the current knowledge about the various molecules that can be applied in promoting white-to-brown adipose tissue conversion and energy expenditure and the cellular mechanisms involved.

Effect of Maytenus ilicifolia Mart.ex. Reiss on spermatogenesis.

The effect of the ethanolic extract of Maytenus ilicifolia Mart.ex. Reiss leaves on spermatogenesis was studied in Swiss mice by evaluating morphological characteristics by light and electron microscopy. The extract was administered at a dose of 200 mg/kg/day intraperitoneally for 20 days, and at a dose of 800 mg/kg/day orally for 30 days. Structural analysis of the germ epithelium showed that treated animals were not noticeably different from control animals. The alterations included some exfoliated immature germ cells, occasional germ cell death (recognized as pyknotic nuclei) and a few vacuolized seminiferous tubules. Ultrastructurally, enlarged lipid droplets were found in Sertoli cells and swollen acrosomes occurred in early spermatids of animals treated with the higher dose. Sperm production indicated that the ethanolic extract of M. ilicifolia leaves did not contain substances sufficient to arrest spermatogenesis.

PIP: Several plant extracts used to regulate female fertility have proved effective for the male reproductive system as well. Maytenus ilicifolia Mart.ex. Reiss, a plant native to parts of South America, has been used as a contraceptive, abortifacient, and emmenagogue by women in Paraguay and Argentina. The present study evaluated the effect of the ethanolic extract of Maytenus ilicifolia Mart.ex. Reiss leaves on spermatogenesis in Swiss mice. The extract was administered at doses of 200 mg/kg/day intraperitoneally for 20 days and 800 mg/kg/day orally for 30 days. Light microscopy revealed apparently normal spermatogenesis in the seminiferous tubules of treated animals. Although the spermatogenic process was not altered, ultrastructural alterations were observed, including some exfoliated immature germ cells, occasional germ cell death, and a few vacuolized seminiferous tubules. Enlarged lipid droplets were found in Sertoli cells and swollen acrosomes occurred in early spermatids of mice treated with the higher dose. However, sperm production indicated that the ethanolic extract did not contain substances sufficient to arrest spermatogenesis. Thus, the indigenous use of Maytenus ilicifolia as a medicinal plant probably does not cause a disturbance of spermatogenesis as a side effect.

Antispermatogenic effect of Achillea millefolium L. in mice.

The effect of an ethanolic extract (200 mg/kg/day, intraperitoneally, for 20 days) and a hydroalcoholic extract (300 mg/kg/day, orally, for 30 days) of Achillea millefolium L. (yarrow) flowers on the spermatogenesis of Swiss mice was studied by evaluating morphologic characteristics with the light and electron microscopes. The alterations observed were exfoliation of immature germ cells, germ cell necrosis, and seminiferous tubule vacuolization. Animals treated with the extracts had an increased number of metaphases in the germ epithelium that might be due to cytotoxic substances or substances stimulating cell proliferation.