March 28th, 2023
Author: Anisha Bhola
Editor: Dr. Shampa Ghosh
Are we all familiar with the concept of Obesity?
Obesity is a pathological condition characterized by atypical or excessive deposition of adipose tissue, which predisposes individuals to an elevated risk of health-related complications. This multifactorial condition arises when an individual’s energy intake through food surpasses their energy expenditure through physical activity. Remarkably, body fat percentage serves as a useful indicator of the extent of adipose tissue accumulation, which in turn heightens the risk of developing various health conditions, including but not limited to obesity, type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease. The pervasiveness of obesity is evident in India, where it affects over a million individuals annually.
How does maternal over-nutrition affect neural circuitry?
Based on the findings from molecular metabolism and experiments conducted by Shrivastava et al., maternal overfeeding during gestation may cause offspring to inherit a predisposition towards obesity and diabetes. This condition results in an alteration of the brain’s neural circuitry, leading to an increased inclination towards consuming highly palatable and unhealthy foods.
Researchers have experimentally observed the link between this bridge and alterations in synaptic input, which can occur in children due to over-nutrition of the mother.
They showed that if a mother is overfed during gestation as well as lactation with High Fat Diet (HFD), it leads to overweight and obese pups. However, the study also revealed that the body weight of these offspring returned to normal when they were weaned onto chow (a cereal-based diet). Additionally, upon exposure to highly palatable and unhealthy foods, the pups became susceptible to diet-induced obesity, leading to subsequent weight gain.
For the experiment, Srivastava et al used a total of six mice out of which three were given a high-fat diet (HFD) and standard chow while the other three were given a low-fat diet (LFD) and standard chow. They were separated and bred with a male mouse that had been maintained on standard chow. So, two experimental groups of mothers were there where in one group mothers consume LFD (mLFD) and in another group mothers consume HFD (mHFD). When pups were born on postnatal day 21 (p21) they were weaned onto chow. At p40 pups were given an acute HFD diet and at p60 chronic HFD diet was given to the pups. After that mice were injected with the light-gated cation channel, channelrhodopsin-2 (ChR2) in the Bed Nucleus of Stria Terminalis (BNST).
They also did electrophysiological, current clamp, and voltage-clamp recordings to find out the following synaptic input alterations to the lateral hypothalamic area.
1) Maternal over-nutrition increases Lateral Hypothalamic Area (LHA) neuronal excitability.
2) Maternal over-nutrition increases excitatory inputs onto BNST neurons.
3) BNST has primary GABAergic connections with LHA and is negatively correlated with early life growth rate.
Over-nutrition during pregnancy alters feeding behavior by modifying such pathways. These results in mice as animal models infer and mirror the condition in humans as humans are also likely to be obese if their mothers are over-nutrition during gestation and lactation. Hence, we can also say that maternal over-nutrition alters the neural circuitry of children and all future generations. These results also showed how the difference in Brain circuitry can create different behaviour just because of different nutrition given to mothers during gestation and lactation.
Results also suggest that one can control whether to be obese or not just by choosing the right nutrition even if born to an over nutrition mother. If one consumes highly palatable food then it will lead to diet-induced obesity.
Extensive studies need to be done to elucidate the matter at hand even in various animal models. Future applications of the studies will help in generating drugs that will be targeted towards the LHA pathway to decrease the overheating and excessive desire for palatable food intake.
REFERENCES
1. Shrivastava K, Swaminathan T, Barlotta A, Athreya V, Choudhry H, Rossi MA. Maternal overnutrition is associated with altered synaptic input to lateral hypothalamic area, Molecular Metabolism, Volume 71, 2023, 101702, https://doi.org/10.1016/j.molmet.2023.101702.
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