Macrophages resident in the WAT secrete factors that stimulate the adipocyte progenitors to produce activin A, a molecule that promotes their proliferation (Christian Dani, Universit?© de Nice Sophia-Antipolis, Nice, France) “ another example of the tight regulatory communication between adipocytes and macrophages that changes balance as stored fat increases. Key pathways in the switch between proliferation of adipocyte progenitors and their differentiation into adult adipocytes are being revealed using a whole genome approach (Evan Rosen, Beth Israel Deaconess Medical Center, Boston, USA).

One obvious way to restore the energy input “ output balance, though one that is often difficult to implement, is to increase energy output. Consequently, there is much excitement about the recent discovery that some human adults have another type of fat, the brown adipose tissue (BAT), which is dedicated to the generation of heat (Sven Enerb?¤ck, University of Gothenburg, G?¶teborg, Sweden). Previously known only in rodents, animals that hibernate and human infants, brown fat cells rapidly take up triglycerides and, through a unique mitochondrial mechanism, convert them to heat rather than the normal synthesis of the energy-rich molecule ATP. Studies on mice are revealing that BAT protects against obesity, insulin resistance and type-2 diabetes (Sven Enerb?¤ck, University of Gothenburg, G?¶teborg, Sweden; Barbara Cannon, Stockholm University, Stockholm, Sweden).

A further discovery makes the presence of brown fat not just lucky for those adults who have it: under certain laboratory conditions, white fat cells can be converted to brown. As the therapeutic implications of this potential are clear, the molecular mechanisms and the requisite conditions that promote this conversion are now under intense investigation (Dominique Langin, Inserm U858, Universit?© Paul Sabatier, CHU Toulouse, Toulouse, France; Christian Dani, Universit?© de Nice Sophia-Antipolis, Nice, France; Bruce Spiegelman, Harvard Medical School, Boston, USA; Stephen Farmer, Boston University School of Medicine, Boston, USA).

Regulation of body weight concerns not only the WAT: the brain is also involved. This level of regulation turns out to be quite subtle, with the hypothalamic and higher brain circuits protecting more against weight loss than against weight gain (Rudolph Leibel, Columbia University, New York, USA). As well as making evolutionary sense, here is a mechanism that supports common experience that it is far easier to gain weight than to lose it! Understanding this complex neural and hormonal regulation may well point to ways to shift the balance towards weight loss. Genetics of course also plays a part and studies of single-gene mutations that affect the functioning of the WAT are helping to dissect the molecular pathways underlying insulin resistance (David Savage, University of Cambridge, Cambridge, UK).

Source: La Fondation Ipsen