Leptin: The Hormone That Can Make You Hungry… or Not

Hello Midlife Mayhem—

Today we’re talking about something that explains a LOT when it comes to fat loss and appetite:

👉 Leptin

And I’ll start with this—

I recently did a podcast on appetite, and while the information was solid… I didn’t fully acknowledge the people who are:

👉 Hungry all the time 👉 Fighting cravings constantly 👉 Being told “just eat less” when it feels impossible

This episode fixes that.

Leptin is your body’s appetite regulator, produced by your fat cells.

👉 More fat = more leptin 👉 Less fat = less leptin

And your brain responds like this:

High leptin:

• Eat less
• Burn more

Low leptin:

• Eat more
• Burn less

👉 Perfect in theory… frustrating in real life.

As you lose weight:

• Leptin drops
• Your brain senses “less stored energy”
• You get hungrier
• Your metabolism slows

👉 This is why those last pounds feel so difficult.

It’s not you. It’s physiology.

This is where it really matters.

👉 You have plenty of leptin… but your brain doesn’t recognize it.

So instead of saying: “we’re fine”

Your brain says: 👉 “we’re starving”

And the result:

• Constant hunger
• Lower calorie burn
• Strong drive to eat

👉 This is not a willpower issue.

These medications reduce appetite—and for many people, that’s life-changing.

But then comes a fork:

• No real habit change
• Appetite returns
• Weight comes back

• Better food choices
• More protein
• Strength training
• New identity

👉 Same tool. Completely different outcome.

Strategically increasing calories (especially carbs) can signal:

👉 “We’re not starving”

This can help:

• Keep fat loss moving
• Reduce metabolic slowdown
• Improve adherence

And yes—

👉 It needs carbs to work properly.

Leptin can:

• Help regulate appetite
• Or completely override it

So if you’ve ever thought:

👉 “Why am I always hungry?”

There may be a real physiological reason.

If appetite has ever felt like a constant battle— this one will connect a lot of dots.

I go live on YouTube every Sunday— breaking all of this down in real time.

👉 Subscribe here: @joanneleecornish

👉 www.joannelee.com

👉 hello@joannelee.com

NNMT, Cancer Risk & 5-Amino-1MQ – Where Science Ends and Assumptions Begin

Alright… this one is interesting.

Because I talk a lot about 5-Amino-1MQ— mainly in the context of fat loss, metabolic health, and keeping weight off long term.

But recently, I was in a conversation with a doctor… and he told me he personally takes it because his mother died from a glioblastoma.

And his reasoning?

👉 It inhibits NNMT 👉 NNMT is involved in certain cancers 👉 So… maybe there’s something there

Now before we go any further—

I am NOT saying 5-Amino prevents or treats cancer. And neither was he.

What he was doing… was taking a known biological pathway and making an informed assumption.

And honestly?

It’s a fascinating one.

NNMT (Nicotinamide N-Methyltransferase) is an enzyme involved in how your body manages:

• Energy production
• NAD+ levels
• Metabolic function
• Aging processes

When NNMT is elevated, it’s associated with:

• Fat storage
• Insulin resistance
• Slower metabolic function
• Lower NAD+ availability

👉 This is why it shows up so strongly in midlife weight gain

And it’s also why I talk so much about 5-Amino-1MQ— because it inhibits NNMT, which can shift the body away from storing fat and toward using energy.

NNMT doesn’t just show up in metabolism.

It’s also upregulated in certain cancers, including:

• Glioblastoma
• Pancreatic cancer
• Bladder cancer
• Ovarian cancer

In these environments, NNMT appears to support:

• Tumor growth
• Cell survival
• Metabolic adaptation

👉 In simple terms: cancer cells may use NNMT to survive.

So researchers have asked:

What happens if we inhibit NNMT?

In early-stage research (cells + animal models), 👉 inhibiting NNMT has shown reductions in tumor growth.

That’s real.

But here’s the key…

We have:

• NNMT is involved in metabolic disease
• NNMT is involved in some cancers
• 5-Amino inhibits NNMT

So the leap becomes:

👉 “Does taking 5-Amino reduce cancer risk?”

And the honest answer is:

We don’t have evidence to say that.

No human trials. No prevention studies.

What we have is a mechanistic connection— and a very interesting one.

Here’s where it gets even more compelling…

NNMT increases with:

• Age
• Obesity
• Insulin resistance

And those same conditions are associated with:

• Higher cancer rates
• More chronic disease
• More metabolic dysfunction

So now we’re looking at a broader picture:

👉 A metabolic environment that becomes more vulnerable over time

And NNMT may be one of the players in that shift.

Not the cause. Not the cure. But part of the story.

This is not a recommendation.

This is not a protocol.

This is simply a lens.

• One enzyme
• One molecule that inhibits it
• Two very different areas of research that overlap

👉 That intersection is worth understanding.

Just remember:

Interesting ≠ proven Mechanism ≠ outcome

If you’ve been following my work, you already know I use and talk about:

• 5-Amino-1MQ
• SLU-PP-332

You can learn more or get them here:

👉 www.joanneleestore.com

Use code:

👉 DAISY for 20% off

⏳ Expires April 1

Insulin Isn’t the Enemy: Why Carbs Might Actually Help You Build Muscle

Show Notes

Before we dive in, a couple of quick reminders.

My Muscle Month program starts March 29, and it only runs once a year. If you’ve been thinking about joining, this is the time. The program walks you through exactly how muscle is built and protected in midlife — including insulin, carbohydrates, mTOR, AMPK, and how to actually use these tools to your advantage.

You can join at musclemonth.com. The cost is $525, and if you’d prefer to split the payment just email me at www.joanneleestore.com.

Now onto today’s topic.

In this episode I talk about insulin, and why it has been given such a terrible reputation in the health and fitness world. For years we’ve heard that carbohydrates spike insulin, insulin stores fat, and therefore carbs must be the problem. And while there is some truth buried in that narrative, the reality is far more interesting.

Insulin is not the villain. It’s actually a tool.

Yes, when insulin is chronically elevated it can absolutely prevent fat loss. A prolonged high-insulin state is one of the biggest reasons people struggle to lose weight, particularly in midlife. Stress, sedentary lifestyles, constant snacking, poor sleep and excessive carbohydrate intake can all push insulin up and keep it there. When that happens, the body simply can’t access stored body fat efficiently.

But that doesn’t mean insulin itself is the problem.

Insulin is one of the body’s key growth signals, alongside protein, testosterone and growth hormone. It helps move nutrients into cells, including glucose and amino acids, which means it plays a direct role in muscle repair, recovery and growth. If someone completely avoids carbohydrates out of fear of insulin, they may actually be removing one of the body’s natural tools for maintaining muscle.

A big part of the conversation in this episode is about environment. Hormones respond to the environment we create. If someone is stressed, sedentary, eating constantly and sleeping poorly, insulin will behave very differently than it will in someone who is active, training, eating strategically and giving the body periods where insulin can come back down.

When used correctly, insulin can actually support both muscle building and fat loss. Timing carbohydrates around activity, especially training, can help direct those carbohydrates into muscle where they’re stored as glycogen rather than fat. Insulin also helps move amino acids into muscle tissue, which is critical for protecting muscle as we age.

I also share a little about my own experience. For many years I ate very low carbohydrate and it worked well for me. But after a major surgery in my 50s where I lost a significant amount of muscle, I had to rethink my approach. Bringing carbohydrates back in strategically allowed me to support muscle again, sleep better, recover better, and overall feel better.

The big takeaway from this episode is simple: insulin is not the enemy. It simply reacts to the environment we create. When we understand how it works, it becomes something we can use to our advantage rather than something we fear.

And if you’d like to go deeper into how all of this works — especially in midlife — Muscle Month starts March 29. You can learn more and sign up at musclemonth.com.

Also, if you’d like to catch the new weekly live sessions, head over to YouTube and subscribe to Joanne Lee Cornish so you’ll get notified when I go live.